Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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DAVID Functional Annotation Table
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integrin subunit beta 3(ITGB3) integrin subunit beta 3(ITGB3) Related Genes Homo sapiens
CHROMOSOME 17,
CYTOBAND 17q21.32,
ENSEMBL_GENE_ID ENSG00000259207, ENSG00000259753,
GENERIF_SUMMARY Distinct domains of alphaIIbbeta3 support different aspects of outside-in signal transduction and platelet activation induced by LSARLAF., Both the high affinity thrombin receptor (GPIb-IX-V) and GPIIb/IIIa are implicated in expression of thrombin-induced platelet procoagulant activity., A naturally occurring point mutation in the beta3 integrin MIDAS-like domain affects differently alphavbeta3 and alphaIIIbbeta3 receptor function., Lateral clustering of platelet GP Ib-IX complexes leads to up-regulation of the adhesive function of integrin alpha IIbbeta 3, Review. Alpha(v)beta3 integrins are involved in vascular repair processes. The challenge is to develop a therapeutic agent that will prove effective in reducing restenosis in humans following percutaneous coronary intervention (PCI)., GPIIb-IIIa complexes are not in an activated conformational state after dissociation of abciximab unless there is an additional source of activation., beta3-Integrin expression was directly up-regulated by HOXA10 in the endometrium, location was observed on or near the cell surface suggesting it might participate in surface membrane transport of iron, A novel 196Leu to Pro substitution in the beta3 subunit of the alphaIIbbeta3 integrin in a patient with a variant form of Glanzmann thrombasthenia prevents GPIIbIIIa from binding fibrinogen when platelets are activated., Unique ability of integrin alpha(v)beta 3 to support tumor cell arrest under dynamic flow conditions (Integrin alpha-v beta-3), Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton, Del1 mediates vascular smooth muscle cell adhesion, migration, and proliferation through interaction with integrin alpha(v)beta(3)., Immunohistochemical analysis of human tumor sections from several organs showed a heterogeneus distribution of CD61 in metastatic cases from colon and breast carcinoma. However, no staining was found in metastasis from melanoma., Relationships between Rap1b, affinity modulation of integrin alpha IIbbeta 3, and the actin cytoskeleton (integrin alpha(IIb)beta(3)), Site-directed mutagenesis of residues on the top surface of the integrin beta3 I-domain that contains a putative ligand binding site identified D158 and N215 as novel residues critical for ligand binding., Factor XIII mediates adhesion of platelets to endothelial cells through alpha(v)beta(3) and glycoprotein IIb/IIIa integrins., A new platelet polymorphism Duv(a+), localized within the RGD binding domain of glycoprotein IIIa, is associated with neonatal thrombocytopenia, collagen receptor glycoprotein VI and alphaIIbbeta3 trigger distinct patterns of receptor signalling in platelets, leading to tyrosine phosphorylation of PLCgamma2 (integrin alphaiibbeta3), Integrin alpha IIbbeta 3 has agonist-specific activation states and causes intrasubunit and intersubunit allosteric effects, Two different beta3 cysteine substitutions alter alphaIIb beta3 maturation and result in Glanzmann thrombasthenia., Integrin-linked kinase transiently associates with and phosphorylates beta3, regulating platelet integrin alphaIIb beta3 in a PI3-kinase dependent manner, Alpha(v)beta(3) integrin engagement enhances cell invasiveness in human multiple myeloma., integrin alphaVbeta3 expression is reduced when ROR alpha is activated in prostate cancer cells, Integrin alphavbeta3. Expression of integrin alpha v beta 3 promotes the metastatic phenotype in human melanoma by supporting specific adhesive, invasive and migratory properties of the tumor cells, Disruption of the long-range GPIIIa Cys(5)-Cys(435) disulfide bond results in the production of constitutively active GPIIb-IIIa (alpha(IIb)beta(3)) integrin complexes., Role for beta3 integrins in human melanoma growth and survival., alpha v beta 3 integrin signaling through Shc recruitment in response to mechanical stimulation in human osteoblasts, regulation of integrin function by CD47 ligands, phosphoinositide 3-kinase C2alpha was found to be differentially regulated by alpha(v)beta(3) engagement, promotion of integrin alpha Vbeta 3-dependent endothelial cell adhesion by PGE2, co-stimulation of G(12/13) and G(i) pathways is sufficient to activate GPIIb/IIIa in human platelets in a mechanism that involves intracellular calcium, Data show clearly that integrin alpha(v)beta(3) interacts with the latency-associated peptide (LAPbeta1 and 3) RGD motif., role in mediating pro-angiogenic activity of CYR61, An autocrine loop of the integrin alpha(V)beta(3)/CD47 receptor complex and thrombospondin-1 is identified as the molecular coupling device between mechanical loading and apoptosis., in patients with endometriosis a significant negative correlation was observed between luminal expression of eNOS and alpha(v)beta(3) integrin and between glandular expression of eNOS and luminal expression of alpha(v)beta(3) integrin, thrombin interacts with alphavbeta3 as demonstrated by direct binding of alphavbeta3 protein to immobilized thrombin., a 17-amino acid sequence is identified as a common epitope for antibodies associated with quinine-induced immune thrombocytopenia, activation state of alphaVbeta3 integrin is an important regulator of the duration of insulin-like growth factor I receptor phosphorylation and this regulation is mediated through changes in the subcellular localization of SHP-2, Ligand binding promotes the entropy-driven oligomerization of this protein, Data show a novel mechanism by which ECM regulates membrane-type 1 matrix metalloproteinase (MT1-MMP) association with beta1 or alphavbeta3 integrins, thus modulating its internalization, activity, and function on human endothelial cells., role of Pro33 polymorphism in enhanced activation of mitogen-activated protein kinase and myosin light chain kinase, integrin alpha5beta1-mediated control of the levels of integrin alphaVbeta3 is important for the distribution of focal contacts, Integrin alphaiibbeta3 plays a role in signal transduction that leads to a defect in leukocyte adhesion, has a role in the early phase of liver metastasis, possible association between the GPIIb/IIIa PIA1/A2 polymorphism and the occurrence of cryptogenic stroke in young patients, data suggest that despite partial disruption of calf-1 or calf-2 domain by mutation in Glanzmann thrombasthenia, glycoprotein IIb/IIIa complex is formed but its transport from the endoplasmic reticulum is impaired, Review. A signal is initiated at the cytoplasmic tail to transform the extracellular domain of alphaIIbbeta3 into a functional receptor for fibrinogen or von Willebrand factor to support platelet aggregation & thrombus formation., thymidine phosphorylase and 2-deoxyribose-induced focal adhesion kinase phosphorylation was blocked by the antibodies to integrins alpha 5 beta 1 and alpha v beta 3, directly linking their migration and signaling components, decreased expression of endometrial integrin alphavbeta3 suggests that functional, but not morphological, endometrial defect may be one of the causes for the patients with unexplained infertility and recurrent IVF-ET failures, Alphavbeta3 integrin expression and pinopode formation in human endometrium are processes closely related to endometrial maturation; unlikely as targets for contraceptive approaches or fertility-promoting strategies, Intercellular calcium communication is primarily mediated by a signaling mechanism operating between this protein, ITGA2B and the adenosine diphosphate purinergic receptor P2Y12., tumstatin binds to alpha v beta 3 integrin in a vitronectin/fibronectin/RGD cyclic peptide independent manner, in megakaryocytes turbulence induces Rap1 activation that controls alphaIIbbeta3-mediated cell adhesion, role of polymorphisms in cardiovascular thrombotic disease [review], Data suggest that this alphavbeta3 binding to alpha5-laminins is involved in the regulation of cellular responses to growth factors known to be involved in epithelial and endothelial development., This study revealed detailed topography of integrins in malignant tumours derived from intercalated acinar segment of salivary gland which might be useful their diagnosis , especially of fine-needle aspiration products or from incisional biopsy., binding of thrombin to GPIbalpha induces fibrin binding to resting alphaIIbbeta3 leading to fibrin-dependent platelet aggregation and clot retraction, that can be selectively inhibited by alphaIIbbeta3 antagonists, results suggest that homomeric associations involving transmembrane domains provide a driving force for integrin activation; results also suggest a structural basis for the coincidence of integrin activation and clustering, the extracellular Ig domain of IAP(CD47), when bound to thrombospondin, interacts with integrin alphaIIbbeta3 and can change alphaIIbbeta3 in a high affinity state without the requirement of intracellular signaling, signaling through JAM-1 and alphavbeta3 is necessary for bFGF-induced angiogenesis., Data provide the first evidence that alphavbeta3 integrin can generate apoptosis-stimulating signals., alphavbeta3 expression in LNCaP (beta3-LNCaP) prostate cancer cells causes increased cdc2 mRNA levels as evaluated by gene expression analysis, and increased cdc2 protein and kinase activity levels, identification of binding site in gamma C-domain of fibrinogen, alpha 5 beta 1 and alpha v beta 3 are both important but cell-specific fibrillin-1 receptors, Low concentrations of agonists resulted in enhanced platelet aggregation in subjects with the GNB3 CC-genotype compared to carriers of a 825T-allele., relationships between the expression levels of CD61, CD63, and PAC-1 on the platelet surface and the incidences of acute rejection and tubular necrosis as well as the recovery of graft function after renal transplantation, analyzed the possible cooperation effect between the PlA2 allele (GPIIIa) and LL genotype (SLC6A4) in the development of myocardial infarction, high prevalence of the HPA-1b allele of beta3 in Glanzmann thrombasthenia, integrin alphavbeta3 cooperates with metalloproteinase MMP-9 in regulating migration of metastatic breast cancer cells, Individuals homozygous for the Leu33Pro polymorphism of the beta3 integrin subunit have an increased cancer risk., Glycoprotein IIb/IIIa has a role in platelet-activating factor-induced platelet activation with protein kinase C activity, the 749EATSTFT756N and 755TNITYRG762T regions of beta3 contribute to the regulation of alphaIIbbeta3 anchorage to the cytoskeleton and platelet spreading to an adhesive surface, beta3 integrin has a role in causing structural rearrangements of the 10-23 DNAzyme, predictions of hydrophilicity, surface accessibility and antigenicity and the three dimensional structure of the beta(3) integrin correlate with autoantibody binding to a recombinant GPIIIa peptide 'B' containing residues 468-691., increased expression of the alpha(v)beta(3) integrin during breast cancer progression can make tumor cells more responsive to malignancy-promoting ligands such as OPN and result in increased tumor cell aggressiveness., the E749ATSTFTN756 region of the beta3-tail stabilizes the binding of soluble and surface-bound ligand to integrin alphaIIbbeta3 via a mechanism that involves the phosphorylation of FAK, integrin alpha(v)beta3 has an important role in bone metabolism and angiogenesis, and in controlling growth of metastatic prostate cancer cells in the bone, proteins regulated by CBFA2 are required for inside-out signal transduction-dependent activation of GPIIb-IIIa, results invoke a model whereby Src is primed for activation by direct interaction with an integrin beta tail, and integrin clustering stabilizes activated Src by inducing intermolecular autophosphorylation, The mutation at the position 29 107 of intron 10, G-->T, in the beta3 genomic DNA was found to induce an aberrant splicing and to be responsible for Glanzmann's thrombasthenia in this patient, activation of the beta subunit I-like domain of integrin beta3 is analogous to that of the alpha subunit I domain, Cysteine residues in the epidermal growth factor domains of the beta3 subunit are important for the ligand binding activity of the integrin alphaIIbbeta3 complex., CD47-alpha(v)beta(3) interactions that lead to integrin clustering are detergent resistant and do not require cholesterol or the transmembrane region of CD47, alphavbeta3 integrin has a role in regulating proliferation and apoptosis of hepatic stellate cells, in the absence of GPIbalpha or following inhibition of thrombin binding to GPIbalpha, there is a reduction in the thrombin-induced calcium flux, beta3 cleavage and micro -calpain activation., analysis of the three-dimensional model of integrin alphaIIbbeta3, APOC3, LPL and GpIIIa genes were found to be associated with BP levels. The contributions of these genes, although modest, are consistent with the polygenic nature of blood pressure levels., integrin alpha(IIb)beta3 adhesive function is regulated by platelet FXIII and calpain, This review discusses the major role played by glycoprotein IIb/IIIa (GPIIb/IIIa) in the regulation of platelet adhesion and aggregation during hemostasis., alpha IIb beta 3 signaling in platelets is regulated by SHIP1 and Lyn kinase, GpIIIa gene polymorphism as a risk factor for stroke caused by large vessel disease in males., results indicate a new interaction partner for the alpha(v)beta(3) integrin, the TGFbetaIIR, in which TGFbeta1-induced responses are potentiated in the presence alpha(v)beta(3) ligands, CD151 is essential for normal platelet function and that disruption of CD151 induced a moderate outside-in integrin alpha(IIb)beta(3) signaling defect, For HPA-1 gene polymorphism, only the HPA-1a/a (PlA1/A1) genotype was observed in Korean population cardiac patients, secondary structure analysis of integrin alphaVbeta3, The HPA-1b (PlA2) allele significantly protected against subarachnoid hemorrhage., analysis of F11R dimerization, phosphorylation and complex formation with the integrin GPIIIa in human platelets, Data suggest that modulating the expression of integrin subunits beta3/5 in human neurons may enhance adenoviral infectivity via the coxsackie-adenovirus receptor., beta3 integrins play important roles during transendothelial migration of PC3 cells while interacting with the matrix underneath the endothelium. These interactions are independent of the ability to cluster beta3 integrins into focal adhesions., CEACAM1 and alpha(v)beta(3) integrin are functionally interconnected with respect to the invasive growth of melanomas, PlA1/A2 polymorphism of platelet glycoprotein IIIa (GPIIIa) has is not implicated in the pathogenesis of type 2 diabetes., A novel 465T-->C (S123P) mutation in exon 3 interfered with the platelet aggregation in a manner similar to Glanzmann's thrombasthenia., Inheritance of the integrin beta3 Leu33Pro polymorphism may increase the breast cancer risk by age 45 in the German population., a novel missense mutation of Ile304 to Asn in addition to the missense mutation His280 to Pro in the integrin beta3 gene as a cause of the absence of platelet alphaIIbbeta3 in Glanzmann's thrombasthenia, The Integrin beta3 receptor is expressed on almost all cells originating from the mesenchyme and seem to mediate several biological processes, including adhesion of osteoblasts to the bone matrix., Mu-calpain is activated in human endometrial cells during hypoxia and that subsequent cleavage of the integrin beta3 cytoplasmic domain may give some adverse effects to the function of human endometrium, Pyk2 is a phosphorylated beta(3) binding partner, providing a potential structural and signaling platform to achieve alpha(V)beta(3) -mediated remodeling of the actin cytoskele, there is a phosphorylation-dependent association between beta(3) integrin and Vav1 which is essential for cell progression to a Rho-dominant phenotype during cell adhesion, integrin alphaIIbbeta3 has a role in mechanotransduction for shear activation of platelets, alphaIIb-mediated outside-in signaling resulting in TxA(2) production and granule secretion is negatively regulated by a sequence of residues in the membrane distal beta3 cytoplasmic domain sequence RKEFAKFEEER., association between early fetal loss and the presence of the PLA2 polymorphism of the ITGB3 gene, Of the 22 Glanzmann thrombasthenia patients studied, mutations were detected in 12 individuals. Of these, 11 were novel mutations., We conclude that the ectodomain of alphaVbeta3 manifests a bent conformation that is capable of stably binding a physiological ligand in solution., This study provides evidence that ITGB3 plays a role in the pathogenesis of asthma and sensitization to mold allergens., dephosphorylation events play a role via serine/threonine phosphatases during the integrin outside-in signaling mechanism, and the Leu(33) --> Pro polymorphism regulates this process, Epidermal growth factor receptor and alphavbeta3 work together as coreceptors for Human cytomegalovirus entry and signaling., variation in ITGB3 in addition to Leu33Pro could contribute to susceptibility to cardiovacular disease and serotonin in a sex-specific manner, Results support the hypothesis that carriers of the GP IIIa PlA2 allele might have an increased risk for acute coronary syndrome in Hungarian population., SHPS-1 negatively regulates platelet function via CD47, especially alpha(IIb)beta(3)-mediated outside-in signaling, TPO integrates G(i), but not G(q), stimulation, supports integrin alpha(IIb)beta(3) activation platelet aggregation independently of phospholipase C but requires PI3-kinase and Rap1B, an apparently silent beta3 mutation results in aberrant splicing and reduced beta3 mRNA and may play a causative role in Type I Glanzmann thrombasthenia, electron tomography analysis of the three-dimensional structure of integrin alphaIIbbeta3 in the active state, PI3-K and calcium oscillation are synergistically operated and form a positive-feedback regulation in integrin alpha(IIb)beta3-mediated outside-in signaling, Gal3ST-2 is involved in tumor metastasis process by regulation of adhesion ability to selectins and expression of integrin alphaV but not beta3, reactive oxygen species produced in platelets significantly affected alphaIIbbeta3 integrin activation, platelet membrane integrins alpha IIb(beta)3 (HPA-1b/Pl) and alpha2(beta)1 (alpha807TT) polymorphisms may have a role in premature myocardial infarction, melanoma cells cross-present, in an alpha v beta3-dependent manner, an antigen derived from secreted matrix metalloproteinase-2 (MMP-2) to human leukocyte antigen A*0201-restricted T cells, integrin alphavbeta6, alphavbeta3, alphavbeta5, alpha5beta1 and alpha9beta1 binding to osteopontin is controlled by specific structural motifs that are recognized by extracellular proteases, Highest expression of alphavbeta3 integrin is associated with metastatic potential of osteosarcoma cells by enhancing the ability of the cells to migrate specifically to the lung, the engagement of alphaIIb beta3 by the C-terminal sequence of the fibrinogen gamma-chain initiates signals that suppress subsequent fibronectin assembly by spread platelets, GPVI and integrin alphaIIb beta3 have roles in signaling during platelet adhesion and platelet aggregation [review], Data show that alpha(v)beta3/Tat interaction triggers the activation of NF-kappaB in endothelial cells in a focal adhesion kinase-, RhoA- and pp60src-dependent manner, and this activation is required for motogenic activity of Tat in endothelial cells., ITGbeta3 subunit cytoplasmic domains require membrane anchorage and the NPXY motif to recruit to adhesion complexes, Data show that protein-tyrosine phosphatase (PTP)-1B is an essential positive regulator of the initiation of outside-in alphaIIbbeta3 integrin signaling in platelets., Glycoprotein IIIa allele has been found in many studies to associate with risk of thrombosis., alphavbeta3 integrin is transiently up-regulated (and activated) in graft arteriopathy, The 177-184 sequence of beta3 is necessary for vitronectin binding to alphaVbeta3., Cells overexpressing beta3 integrin can bind human ADAM12 via beta3 integrin., PI3K and granular released ADP in coordinating the feedback regulations in integrin alpha(IIb)beta3-mediated platelet activation, beta3 knockout mice transfused with wild-type platelets generated specific anti-beta3 antibodies which were able to induce thrombocytopenia in wild-type mice., ITGB3 gene polymorphisms is associated with breast cancer, Integrin beta(3) Leu33Pro homozygotes have an increased risk of ovarian cancer., analysis of platelet integrin alphaIIbbeta3 structure and function (review), the beta3 integrin gene is the direct target of NFAT1 in osteoclast formation, Outside-in signaling through integrin alpha2beta1 triggered inside-out activation of integrin alphaIIbbeta3 and promoted fibrinogen binding. (alpha2beta1 AND integrin alphaIIbbeta3, three beta-propeller mutations do not affect the production of pro-alpha(IIb), its ability to complex with beta3, or its stability, but do cause variable defects in transport of pro-alpha(IIb)beta3 complexes from the endoplasmic reticulum to the Golgi, Our results did not show the causative relationship between the existence of platelets GP IIIa mutations and venous system thrombosis in the women in labor., Expression of integrins alphavbeta1, alphavbeta3, and alphavbeta5 in cerebral arteriovenous malformations and cavernous malformations. (Integrins alphavbeta1, alphavbeta3, and alphavbeta5), the signal interaction between IGF-1R and alpha(v)beta3 integrin plays an important role in promoting the development and progression of cervical cancer, cardiotoxin A5 binds to alpha(v)beta3 integrin and inhibits bone resorption, The endometrial expression of beta3 integrin subunit is reduced in the presence of tubal phimosis or hydrosalpinx, during the window of implantation., Inhibition of alphaIIbbeta3 activation by NAD(P)H oxidase inhibitors and superoxide scavengers was independent of NO/cGMP signaling demonstrating a direct role of platelet NAD(P)H oxidase-generated ROS for integrin alphaIIbbeta3 activation., T cells from kidney allograft recipients can express significant amounts of alpha-beta 3 integrin (CD41/CD61., These results establish the beta3 gene as a direct target of NFATc1 in RANKL-dependent osteoclast formation., Increase in the affinity of alphaIIb beta3-mediated cell adhesion through binding to calcium- and integrin-binding protein following agonist stimulation is impaired in patients because of mutations., the Pro33 isoform of purified integrin alphaIIbbeta3 has increased fibrinogen and prothrombin binding, P-selectin expression, but not activated GPIIb/IIIa, is enhanced in ADP-activated platelets in the inflammatory stage of Takayasu's arteritis. SELP may play a significant role in the inflammatory and thrombotic responses associated with intractable TA, Results describe the multifunctional behavior of integrins, including integrin beta 3, based on their modification potential at hydroxyl groups of amino acids as a source of interplay., while the C-terminal region of the alpha(IIb) tail minimally influences alpha(IIb)beta(3) activation, the C-terminal region of the beta(3) tail is critically involved, Data showed that ITGB3 and SLC6A4 expression levels are correlated., analysis of metal-binding sites in the integrin beta3 A-domain, we show that a coding variant of ITGB3 is associated with autism susceptibility in a large multiplex sample (P = 0.00082), and that this variation has different effects in males and females (P = 0.0018)., integrin alpha3beta1 is a receptor for the alpha3NC1 domain and transdominantly inhibits integrin alphavbeta3 activation, binding of CXCL12 to its receptor leads to enhanced expression of alpha5 and beta3 integrins, binding of resveratrol to integrin alphaVbeta3, principally to the beta3 monomer, is essential for transduction of the stilbene signal into p53-dependent apoptosis of breast cancer cells., PET Molecular imaging of alpha(v)beta3 expression with [18F]Galacto-RGD in humans correlates with alpha(v)beta3 expression as determined by immunohistochemistry., Results suggest that shear stress directly modulates alpha(IIb)beta(3) function and that the shear-induced signaling contributes to regulation of platelet aggregation by directing the release of constraining cytoskeletal elements from the beta(3)-tail., beta3 integrin alters TGF-beta signaling in mammary epithelial cells via Src-mediated TbetaR-II tyrosine phosphorylation, which significantly enhanced the ability of TGF-beta to induce epithelial to mesenchymal transition and invasion., interactions between alphaIIbbeta3 & ligands echistatin & fibrinogen's gamma-module; studies differentiate priming ligands, which bind to resting receptor & perturb its conformation, from regulated ligands, where binding-site remodeling must first occur, analysis of platelet integrin alphaIIbbeta3 mutations that may play a role in Glanzmann thrombasthenia, Protein kinase C delta is positively regulated by platelet alpha IIb beta 3 outside-in signaling in platelet function., Tyrosine phosphorylation of beta3 promotes integrin outside-in signaling, by which the timing and location of calpain cleavage of integrins are dynamically regulated., N-cadherin and beta3 integrin expression correlates with progression to advanced-stage melanoma., platelet alphaIIbbeta3 is activated by an exogenous peptide corresponding to the transmembrane domain of alphaIIb, The transition from a locally invasive phenotype to a metastatic phenotype may be primed by the elevated expression of alpha(v)beta(3) receptors in prostate cancer cells., Cell surface expression of alphavbeta5 resulted in an attenuation of alphavbeta3-mediated migration on vitronectin, results demonstrate differential modes of regulation of Dok1 and Dok2 in platelets, and raise the possibility that Dok2 plays an important role in integrin outside-in signaling through a physical and functional interaction with integrin alphaIIbbeta3, Transduction of beta3 integrin subunit cDNA confers on human keratinocytes the ability to adhere to denatured collagen (gelatin)., identifies integrin alphaVbeta6 as a novel cellular receptor for fibrillin-1 with a K(d) of approximately 0.45 mum, type I collagen induction of MT1-MMP-mediated MMP-2 activation is repressed by alphaVbeta3 integrin in human breast cancer cells, beta3 integrin in MDA-MB-231 breast cancer cells may lead to increased MMP-2 expression and activity and might contribute to the enhanced invasive potential observed, SLC6A4 and ITGB3 gene interactions have roles in autism etiology and in serotonin level determination, The ITGB3_Leu33Pro polymorphism may potentially increase the risk of ovarian cancer in Polish women with an inherited BRCA1 mutation., Inhibition of integrin alphavbeta3 leads to abrogation of migration of HSC stimulated with PDGF-BB and to an antifibrogenic gene expression pattern., Individuals homozygous for the integrin beta3 Leu33Pro polymorphism have a two-fold risk of hip fracture, mainly confined to postmenopausal women., T cells epitopes on Glycoprotein IIIa., data suggest that the Pl(A2) polymorphism is a genetic determinant of ischemic stroke in a selected high-risk hypertensive population, the surface density of fibrinogen affects alpha II b beta 3-mediated platelet signaling, adhesion, and spreading, All patients with ISSNHL should undergo a comprehensive hematologic investigation of inherited and acquired prothrombotic factors, including platelet and V Leiden mutations, to identify a subset of patients at high risk of recurrent HL., in patients with stable coronary artery disease, an increased platelet reactivity after exercise, is specifically associated with an increased expression of platelet GP IIb/IIIa receptor, No association between GpIIIa polymorphism with either type 2 diabetes or ST elevation acute myocardial infarction., Prostate cancer cells expressing fully functional but not dysregulated alphavbeta3 integrin are able to control their own adherence and migration to bone matrix, functions that facilitate tumor growth and control bone lesion development., This is the first demonstration that NO directly regulates integrin beta(3) phosphorylation., Discussion of recent developments in elucidating the mechanism of integrin activation, with particular focus on the platelet integrin alphaIIbbeta3, is provided in this review, activation of ITGB3 transcription required a HoxA10 domain that was not identical to the "hexapeptide" that mediates interaction of Hox and Pbx proteins, Necl-5 has a critical role in integrin alphavbeta3 clustering and focal complex formation, integrins alphaLbeta2 and alphaIIbbeta3 are activated by mutation of a conserved asparagine in the I-like domain, OPN plays a crucial role for tumor growth and angiogenesis of human lung cancer cells in vivo by interacting with alphavbeta3 integrin., Endothelial cell integrin alphaV beta3 is involved in sickle cell red blood cell adhesion., Data show that in bullous pemphigoid, beta3 integrins was detected mainly in basal keratinocytes and in inflammatory infiltrates in the dermis., LOX-1 is important for ADP-stimulated inside-out activation of platelet alpha(IIb)beta(3) and alpha(2)beta(1) integrins, Results suggest that CTGF plays a crucial role in migratory/invasive processes in human breast cancer by a mechanism involving activation of the integrin-alphavbeta3-ERK1/2-S100A4 pathway., Significant associations between single nucleotide polymorphisms in ITGB3 and asthma, wheezing, and IgE levels suggest an early role for this gene in the development of asthma and allergy., Glycoprotein IIIa (GPIIIa, platelet antigen A1 and A2) polymorphisms that contribute to resistance or augmented response to aspirin are rare in the Chinese population., HPA-3b homozygotes have a tendency to develop ST segment elevation myocardial infarction instead of non-ST segment elevation infarction or unstable angina in acute coronary syndrome., Expression of the human ITGB3 subunit in mouse smooth muscle cells enhances IGF-I-stimulated signaling and cell proliferation., separation of transmembrane domains is required for integrin outside-in signal transduction, establishes alphavbeta3 integrin as one key component of the transendothelial migration process of tumor cells, and as a potential target for anti-metastatic therapy, Regions of alpha(IIb) and beta(3) cytoplasmic tails, together with membrane segments of the subunits, contact each other to form a complex which restrains the integrin in a resting state. It is unclasping of this complex that induces integrin activation., c-Src controls functional association between integrin alphav-beta3 and VEGFR-2 via integrin beta3 phosphorylation., The PIA2 allele did not alter the beneficial effect of statins on blood coagulation., Beta2-integrins and acquired glycoprotein IIb/IIIa (GPIIb/IIIa) receptors cooperate in NF-kappaB activation of human neutrophils, preliminary findings show that the HPA-6 A/B genotype is a risk factor for autoimmune thrombocytopenia in systemic lupus erythematosus, The proapoptotic ITGB3 cytoplasmic domain is rarely mutated in common human cancers and may not play an important role in the development of the cancers., Endometrial integrin beta3 and LIF expressions in the peri-implantation phase were significantly lower in stimulated cycles (including both moderate and high responders) compared to natural controls., Structural rearrangements undergone by integrin alpha(IIb)beta(3) after platelet activation were tested., effects of EDTA on GPIIb-IIIa dissociation and loss of adhesive functions are largely but not completely reve, macrophage migration inhibitory factor directly up-regulates alphavbeta3 integrin and VEGF expression in human endometrial Ishikawa cells, analysis of Src and C-terminal Src kinase interactions in integrin alphaIIbbeta3-mediated signaling to the cytoskeleton, Our findings show that A2/A2 homozygosity is associated with an increased risk of visual loss due to anterior ischemic optic neuritis in giant cell arteritis., Truncated beta3 may act as an anti-integrin and play a crucial role in cell migration, which is an important process in tumor invasion and metastasis., platelet glycoprotein IIb-IIIa number (evaluated as maximal binding of (125)I-labelled antibody CRC64) varied from 40.5 to 80.8 x 10(3) per platelet with no significant influence of platelet glycoprotein III a(GP IIIa) genotype., Fourteen of the antibodies reacted with a 29-kDa GPIIIa fragment comprising only the GPIIIa hybrid and plextrin-semaphorin-integrin homology domains, The specificity-determining loop was removed from the betaA domain & the mutations for HPA-4b,& -8,-6, -7, -10,-11,& -16bw antigens were introduced. The structural basis for their reactions with HPA-4 & HPA-bw antibodies was determined., oxidant systems external to platelets did not activate GP IIb/IIIa receptors while increased intra-platelet iron was associated with appearance of cytosolic oxidizing species and with GP IIb/IIIa receptor activation, The precise nature of the integrin beta 3 domains involved in the HPA-1a epitopes was studied by creating 8 soluble peptides & modeling their structures & interations with HPA-1a antibodies. Residues outside the PSI and hybrid domains are required., The ITGB3 GCC-Pro33 haplotype was associated with enhanced vWF activity, which may indicate ITGB3 haplotype influences endothelial function., the studies demonstrate that Vbeta3 is a cellular receptor mediating both the cell adhesion and entry of KSHV into target cells through binding the virion-associated gB(RGD)., a structural change in the conformation of anti-GPIIIa49-66 antibody contributes to its binding to the beta3 integrin and subsequent antibody-induced platelet fragmentation and aggregate dissolution, Polymorphisms in human platelet alloantigen (HPA)-1 and HPA-3 (GPIIb/IIIa), HPA-2 (GPIb/IX), HPA-4 (GPIIIa) and HPA-5 (GPIa/IIa) were found to be associated with the symptoms and recurrence of ischemic stroke., Report observed that alphav-beta3 integrins and Focal Adhesion Protein-Tyrosine Kinases co-localize and that fibrillin filament attachment sites to endothelial cells merge with these molecules., Novel ancestral mutation found in a cluster of Jordanian Glanzmann thrombasthenia patients disrupts a conserved Cys549-Cys558 bond which results in reduced production of constitutively active alpha IIb beta 3., Interleukin-2, interleukin-12, and interferon-gamma levels and risk of young adult Hodgkin lymphoma, uPAR is required to activate alphavbeta3 integrin in podocytes, promoting cell motility and activation of the small GTPases Cdc42 and Rac1, platelet activation and aggregation is regulated by MMP-2 that specifically interacts with integrin alpha(IIb)beta(3), Upon phosphorylation of Tyr 747 in the beta3 integrin tail, however, Dok1 then binds much more strongly than talin., Real-time PCR showed that ETOH significantly altered the expression of genes involved in cell adhesion. There was an increase in the expression of alpha and beta Laminins 1, beta Integrins 3 and 5, Secreted phosphoprotein1 and Sarcoglycan epsilon., the beta3 membrane-proximal and -distal residues cooperatively regulate talin-mediated alpha IIb beta3 activation., Functional and computational studies of the ligand-associated metal binding site of ITGB3 are reported., Data show that integrin beta3 and VEGF expression can synergistically enhance tumor angiogenesis, and may play a crucial role in invasion and metastasis of gastric carcinoma., Tyr178 of beta3 is critical for alphaIIb maturation and macromolecular ligand binding to alphaIIbbeta3, There was a significant association between the PlA2 polymorphism of GPIIIa and the risk of thrombosis in patients with HIT antibodies., tyrosine phosphorylation of GIT1 by Src kinases may regulate cytoskeletal reorganization downstream of alpha(IIb)beta(3) by bringing the Rac guanine nucleotide exchange factor betaPIX to the vicinity of the integrin, data show that the integrin beta 3 262T>C silent mutation is not restricted to a single family, as initially suggested, Thermodynamic data demonstrate that entropy is the dominant factor stabilizing lphaIIbbeta3, Integrin alpha v beta 3 plays a critical role in the S1P-stimulated chemotactic response of ECs., The shear-induced G(2)/M arrest and corresponding changes in G(2)/M regulatory protein expression and activity were mediated by alpha(v)beta(3) and beta(1) integrins through bone morphogenetic protein receptor type IA-specific Smad1 and Smad5., T(3) and T(4) hormones rapidly stimulate ERK activation in MG-63 cells via integrin alpha(V)beta(3) and that one functional effect of this ERK activation is increased DNA synthesis, In conclusion, agglucetin, acting as a survival factor, promotes endothelial adhesion and angiogenesis by triggering alphavbeta3 signaling through FAK/phosphatidylinositol 3-kinase (PI3K)/Akt pathway., The numbers of antibody-binding sites of CD41, CD41a, CD41b, and CD61 on platelets of aplastic anemia patients and in idiopathic thrombocytopenic purpura patients, the numbers of sites for CD41 and CD41a were less than in normal controls., support an unsuspected role of alphaIIbbeta3/serotonin transporter(SERT)associations as well as alphaIIbbeta3 activation in control of SERT activity in vivo, nature of the lipid headgroup affected only the intracellular part of the transmembrane helix, indicating that an asymmetric lipid distribution is not required for studying the beta3 transmembrane segment, Mn(2+) simultaneously modulates the thiol isomerase activity of protein disulfide isomerase that is bound to alpha(V)beta(3) and induces its transition to the ligand-competent state, suggesting an alternative mechanism of integrin regulation, RN181 associates with the platelet-specific integrin alphaIIbbeta3 in human platelets through the conserved alphaIIb cytoplasmic KVGFFKR motif., Protein phosphatase 2Ac (alpha) can negatively regulate integrin alpha(IIb)beta(3) signaling by suppressing the ERK1/2 signaling pathway, This study evaluated whether there was an association between 2 polymorphisms--the platelet glycoprotein (GP) IIIa PlA1/A2 and the endothelial nitric oxide synthase gene and a risk for nonvariceal upper GI bleeding in patients taking low-dose aspirin., Data show that in preeclamptic pregnancies, histamine does not stimulate expression of integrin alphaVbeta3, as it does in uncomplicated pergnancies., Infertile women with isolated polycystic ovaries are deficient in endometrial expression of osteopontin but not alphavbeta3 integrin during the implantation window., results demonstrate that TGFbeta1 induces alphavbeta3 integrin expression via a beta3 integrin-, c-Src-, and p38 MAPK-dependent pathway, ROCK-dependent actomyosin-driven contractility is a critical determinant for the regulation of the interaction between Necl-5 and integrin alpha(V)beta(3)., HCMV-induced angiogenic response depended on viral binding to and signaling through the beta(1) and beta(3) integrins and the EGFR, via their ability to activate the phosphatidylinositol 3-kinase and the MAPK signaling pathways, Show that the Pl(A1/A2) polymorphism of Gp IIb/IIIa primarily affects the aggregation of platelets to monocytes in males., Data show no dramatic height change upon Mn(2+)-induced activation of membrane-bound integrins when compared with an inactive integrin control group., The results suggest that the intensity levels of platelet CD61 were elevated and associated with clinical phases and disease severity in patients with hemorrhagic fever with renal syndrome, CRP at levels found during episodes of inflammation directly binds to the activated form of alphaIIbbeta3 and inhibits platelet aggregation., integrin alphavbeta3 binding to FGF1 plays a role in FGF1 signaling, Results identify kindlin-2 as a novel regulator of integrin beta3 activation; it functions as a coactivator., ITGB3 (beta3) DNA from a Va(a)-positive individual were sequenced and a single-nucleotide polymorphism (C622>T) in exon 5, resulting in the replacement of threonine with methionine at residue 195 was identified., Osteoblast-derived BMP-2 act through Akt and ERK, which in turn activates IKK alpha/beta and NF-kappaB, resulting in the activations of beta1 and beta 3 integrins and contributing the migration of prostate cancer cells., vitronectin and integrin beta(3) contribute to the initiation of TLR2 responses, osteopontin, Talin recruitment to alphaIIbbeta3 by RIAM mediates agonist-induced alphaIIbbeta3 activation, with implications for hemostasis and thrombosis., talin IBS2 binds to the same face of the beta3 subunit cytoplasmic helix as the integrin alphaIIb cytoplasmic tail helix, suggesting that IBS2 can only interact with the beta3 subunit following integrin activation., integrins alphavbeta3 and alpha4beta1 may serve as receptors for sPLA2-IIA and mediate pro-inflammatory action of sPLA2-IIA, Ligand binding to platelet alphaIIbbeta3 induces integrin cytoplasmic domain-dependent phosphorylation of FcgammaRIIa, which then enlists selected components of the immunoreceptor signaling cascade to transmit amplification signals into the cell., human umbilical vein endothelial cells adhere to immobilized CXCL4 through alphavbeta3 integrin, and also through other integrins, such as alphavbeta5 and alpha5beta1, GPIIIa Pl(A2) allele may be a genetic factor that contributes to the risk of sudden death from myocardial infarction in the absence of known risk factors, The presence of GPIIIa on this circulating trophoblast cellular material could be the source of HPA-1a alloantigen causing primary immunization of susceptible primigravidae, Factor XIII V34L, PAI-1, GPIIIa L33P, MTHFR C677T and MTHFR A1298C frequencies of genetic polymorphisms were found to be significantly higher among patients with idiopathic portal hypertension, the 4 biomarkers CLU, ITGB3, PRAME and CAPG may be used as prognostic factors for patients with stage III serous ovarian adenocarcinomas., The alphaIIb G236E mutation causes Glanzmann's thrombasthenia by impairing the association with beta3 during biogenesis of the receptor., UV-C appears to activate alphaIIbbeta3 not by affecting intracellular signal transduction, but by reduction of disulfide bonds regulating integrin conformation., SDF-1alpha enhances the invasiveness of chondrosarcoma cells by increasing alphavbeta3 integrin expression through the CXCR4/ERK/NF-kappaB signal transduction pathway., The apo(a) component of Lp(a) signals through integrin alphaVbeta3 to activate endothelial cells., alpha3 integrin, despite its ability to respond to alternate ligands after wounding, does so through a single structure, the filopodia., Splenic macrophages that take up opsonized platelets via FcgammaRI are major APCs for cryptic GPIIb/IIIa peptides, and are central to the maintenance of anti-platelet autoantibody production in ITP patients, This report analyzed the molecular effects of an A>T substitution leading to an amino acid change, D217>V, in the beta3 integrin gene identified in patients with variant Glanzmann Thrombasthenia., four polymorphisms, GPIIIa, TAFI 147Ala>Thr, methylene tetrahydrofolate reductase (MTHFR) 677 C>T, and MTHFR 1298 A>C, showed significant association with Asian-Indian stroke patients below 15 years of age, ITGA2 807C>T polymorphism may be associated with reduced colorectal cancer risk., Mutation of the clasp region of alphav or beta3 results in a constitutively activated integrin, confirming the role of the extracellular clasp in restraining integrin activation., These results demonstrate that integrin alphavbeta3-mediated transcriptional regulation of MMP-9 and TIMP-1 is critical for suppressing the ovarian cancer cell invasion., VWF strings bind specifically to integrin alpha(v)beta(3) on human endothelial cells, alpha(IIb)beta(3) provides a constitutive presence of factor H on platelets; activation of platelets increases platelet-bound factor which perhaps involves other binding sites for factor H on platelets., Glutathione regulates integrin alpha(IIb)beta(3)-mediated cell adhesion under flow conditions., The genetic polymorphism glycoprotein IIIa leu33pro was significantly associated with CHD., Analogous to EAE, in subjects with MS, we found increased expression of Opn in DCs and increased expression of the Opn receptors CD44, beta(3), and alpha(v) on T cells., Rationally designed integrin beta3 mutants stabilized in the high affinity conformation., M6P/IGF2R controls cell invasion by regulating alphaV integrin expression and by accelerating uPAR cleavage, leading to the loss of the urokinase/vitronectin/integrin-binding site on uPAR., HPA-1a alloantibodies have a direct effect on endothelial cell spreading and monolayer integrity., in cutaneous nodular melanomas, necrosis was associated with increased tumor thickness, tumor ulceration, vascular invasion, higher tumor proliferation and apoptotic index, increased expression of alphavbeta3 integrin & poor patient outcome, analysis of how the different antiangiogenic potential of resveratrol stereoisomers is related to their different capacity to affect alphavbeta3 integrin function, Integrin beta3, like E-cadherin, may be also a suppressor gene down-regulating invasive features of ovarian cancer cells in SKOV3 cell subclones., Ligation of alpha(IIb)beta(3) by immobilized ligands during platelet adhesion induces a transmembrane conformation change in the integrin, resulting in unclasping of the complex between the membrane-proximal parts of cytoplasmic tails., Transient expression of integrin beta(3) in SMMC-7721 resulted in an enhanced level of apoptosis and suppression of colony formation., pneumococci exploit the vitronectin-alphavbeta3-integrin complex as a cellular receptor for invasion and this integrin-mediated internalization requires the cooperation between the host signalling molecules ILK, PI3K and Akt., data suggest that alpha(v)beta(3) is a key molecule that determines the stimulatory or inhibitory effect of pleiotrophin on cell migration, H. pylori ureB antibody could cross-react with human platelet GP IIIa and partly inhibit platelet aggregation. UreB may be a crucial component of H. pylori involved in the pathogenesis of a subset of ITP., Eptifibatide-dependent antibodies engage the integrin beta3 subunit so that FcgammaRIIa and its downstream signaling components become activated, resulting in thrombocytopenia and a predisposition to thrombosis., Beta3 integrin expression within uterine endometrium may have a role in unexplained infertility, Pyk2 is a critical signalling molecule downstream of beta3 integrin tyrosine phosphorylation and mediates Vav1 recruitment to accomplish actin reorganization necessary for adhesion, Data show that cilengitide activated cell surface alphaVbeta3, stimulated phosphorylation of FAK, Src and VE-cadherin, increased cell permeability and decreased cell adhesion in endothelial cells., gene-expression levels of the key angiogenesis molecules VEGF and integrin beta3 were lower in neuroendocrine tumors than in colorectal liver metastases and were highly variable, These results confirm the impact of polymorphism A2 (PLA2) in platelet glycoprotein IIb/IIIa on recurrent spontaneous abortion in the period of 10 to 20 weeks of gestation., Reduced ITGB3 expression is reported in platelets hyposensitive to catecholamines when activated with TRAP., The active site within the Sdc1 core protein was identified and a peptide inhibitor called synstatin (SSTN) that disrupts Sdc1's interaction with alpha(v)beta(3) and alpha(v)beta(5) integrins was derived., Glycoprotein IIB/IIIA inhibitor to reduce postpercutaneous coronary intervention myonecrosis and improve coronary flow in diabetics, only indirect evidence of replication (using LD-tagging SNPs) was observed for three genes (PHF11, IL10, and ITGB3)., The structurally unique, highly conserved integrin alphaIIbbeta3 transmembrane complex rationalizes bi-directional signalling and represents the first structure of a heterodimeric TM receptor complex., HPA-3 but not HPA-1 polymorphism may be one of the inherited risk factors associated with the susceptibility of hantavirus infection and the disease severity of HFRS., Three heterozygous mutations were identified in the genes encoding platelet integrin receptor alphaIIbbeta3 in a patient with an ill defined platelet disorder, Data demonstrated significantly upregulated integrin-linked kinase as a function of alphavbeta3 in two ovarian cancer cell lines, and proved co-localization at the surface of alphavbeta3-overexpressing adherent cells., The novel autosomal dominant macrothrombocytopenia associated with platelet dysfunction raises interesting questions about the role of integrin beta(3), and its betaTD domain, in platelet formation and function., The GpIIIa A1/A2 polymorphism is not a risk factor of aneurysmal subarachnoid haemorrhage in a Polish population., The conformational dynamics of the I-like and Hybrid domains from the beta3 integrin headpiece showed that these two helices function in tandem to initiate large-scale, interdomain conformational transition apparent in integrin activation and signaling., Data show that intermediate filament recruitment to focal adhesions in endothelial cells requires beta3 integrin, plectin and the microtubule cytoskeleton, and is dependent on microtubule motors., The results suggest that Greek carriers of the HPA-1b allele with hypertension may be at increased risk for developing end-stage renal disease., These data strongly indicate that KAI1 may suppress ovarian cancer progression by inhibiting integrin alphavbeta3/vitronectin-provoked tumor cell motility and proliferation as important hallmarks of the oncogenic process., mutations in platelet GlyIIIaA1/A2 were found in patients with sudden sensorineural hearing loss and cardiovascular thrombotic disease, The regulation of EC junctional integrity involves the coordinated and dynamic modification of localization and activity of junctional stabilizers such as the integrin beta(3) and the destabilizer, JAM-C., Activating effect of PLAA1/A2 polymorphism of GPIIIa gene and 677T/T polymorphism of MTHFR gene on morphofunctional state of platelets is proved., Comparison of frequencies of genotypes of polymorphism A1/A2 of GPIIb/IIIa gene in combined sample of population and group with SCD revealed in SCD group lowering of portion of A2/A2 homozygotes, LAMC2, LAMA4, ITGB1, ITGB3, RSPA and MMP2) are overexpressed in angiotropic melanoma cells vs. non-angiotropic melanoma cells from the same tumor, OPN enhances the migration of chondrosarcoma cells by increasing MMP-9 expression through the alphavbeta3 integrin, FAK, MEK, ERK and NF-kappaB signal transduction pathway., PAI-1-mediated regulation of alphavbeta3 integrin is critical for the control of TGFbeta signaling and the prevention of fibrotic disease., GPIIIa PlA2 polymorphism was frequent (27.5%), but the homozygous variant was very infrequent (0.5%). The presence of PLA2 had no influence on peri-procedural or one-year clinical outcomes., Data show that overexpression of CAR in human epithelial cells leads to increased basal activation of p44/42 MAPK and of beta1 and beta3 integrins, and that this is required for efficient Ad5 infection., Multiple approaches converged on the same structure of the resting integrin's transmembrane heterodimer, and this conformation likely reflects the integrin's native structure., High loading dose of clopidogrel is unable to satisfactorily inhibit platelet reactivity in patients with glycoprotein IIIA gene polymorphism, In metastatic brain lesions carrying activated alpha(v)beta(3), VEGF expression is controlled at the post-transcriptional level and involves phosphorylation and inhibition of translational respressor 4E-binding protein (4E-BP1)., Proteins beta3 integrin, Vav3, Plekhm1, and Src, implicated in attachment defects, had normal exon sequences in a new type of osteopetrosis., High expression of integrin beta3 and OPN in ectopic endometrium of adenomyosis may cause endometriotic lesions., the SLC6A4 and ITGB3 gene interaction may have a role in autism, inhibition of integrin beta3 in radioresistant pancreatic cancer cells could enhance adenovirus-mediated gene therapy., Cell adhesion to tropoelastin is mediated via the C-terminal GRKRK motif and integrin alphaVbeta3, review focuses on the structure and function of the beta3 integrins, in particular alphaIIbbeta3, with reference to other integrins where relevant.[review], Integrin beta3 interacts with Galectin-3 in regulating endometrial cell adhesion., Altogether these data suggest that integrins alpha2 and alpha v beta 3 do not play a major role in the rotavirus entry process., Emphasizing the postulated role of myeloma cells in multiple myeloma bone disease; their osteoclast-like activity is regulated, at least in vitro, by the beta(3) subunit of the integrin., Results demonstrated that the growth inhibition of HEC1A cells by GnRH-I or GnRH-II is involved in the activation of integrin-FAK and ERK1/2 and p38 MAPK pathways., Expression of beta1 and beta3 integrins was detected mainly in basal keratinocytes in dermatitis herpetiformis and bullous pemphigoid., 22 novel mutations were identified in 45 unrelated Glanzmann thrombasthenia patients. Analysis of family members showed heterozygous mutations in all families, Periostin mediates vascular smooth muscle cell migration through the integrins alphavbeta3 and alphavbeta5 and focal adhesion kinase (FAK) pathway, These data are the first demonstration of conformational coupling of the integrin alphaVbeta3 leg and head domains, and suggest that inside-out activation may involve conformational changes other than the postulated switch to a genu-linear state., Smooth muscle cell hyperplasia in stricturing Crohn disease is regulated by increased endogenous IGF-I and alphaVbeta3 integrin ligands that regulate augmented proliferation and diminished apoptosis, initial activation-independent platelet adhesion to VWF via GPIb is resistant to NO, however, NO inhibits GPIb-mediated activation of alpha(IIb)beta(3) and MLC leading to reduced platelet spreading and aggregation., In a Croatian population, the gene frequencies of the HPA-1 alleles are 1a-0.854 & 1b-0.146., The authors demonstrate that the F0 domain of kindlin-1 is required for the ability of kindlin-1 to support talin-induced alphaIIbbeta3 integrin activation and for the localization of kindlin-1 to focal adhesions., while a point mutation in the clasp interface modestly activates alphaIIb beta3, additional mutations in the transmembrane interface have a synergistic effect, leading to extensive integrin activation, Data show that leberagin-C can inhibit the adhesion of melanoma tumour cells on fibrinogen and fibronectin, by interfering with the function of alphavbeta3 and, to a lesser extent, with alphavbeta6 and alpha5beta1 integrins., This study shows that alpha(v)beta(3)-integrin expression on tumor cells actually slows tumor progression and acts as a tumor suppressor., Data show that under basal conditions, sphingosine kinase-1, integrin alpha(v)beta(3), and CD31 exist as a heterotrimeric complex which is required in SK-1-mediated endothelial cell survival., BCL-6-transfected breast cancer cell lines expressed significantly higher levels of CXCR4, Itgbeta-3 and FLT-1., An A-to-C SNP at Nt 487 in exon 3 (lysine-to-glutamine substitution at position 137) & a G-to-A SNP at Nt 1960 of exon 11 (glutamic acid-to-lysine substitution at position 628) were associated with neonatal alloimmune thrombocytopenia., alphav beta3 integrin may, in part, negatively regulate VEGF signaling by sequestering NRP1 and preventing it from interacting with VEGFR2, Results describe the role of the membrane distal region of human beta(3) integrin cytoplasmic tail in platelet aggregation, secretion, alpha(IIb)beta(3) activation and fibrinogen binding., The ITGB3 Leu33Pro polymorphism does not modify breast or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers., suggest that a divalent metal-ion coordination was a common driving force for the formation of both SDV/alpha v beta 3 and RGD/alpha v beta 3 complexes., GPIIb/IIIa and alphavbeta3 integrins are important mediators in the pathology of cervical cancer., Oscillatory shear stress induces osteoblast-like cell proliferation through activation of alpha(v)beta(3) and beta(1) integrins and synergistic interactions of FAK and Shc with PI3K, leading to the modulation of ERK and Akt/mTOR/p70S6K pathways., Oxidatively modified fibrinogen showed less binding activity than native fibrinogen to GpIIb/IIIa coated micro beads and human platelets whereas slightly higher binding capacity to ADP induced stimulated platelets, Patients with VWD carrying defective alleles of ITGB3 (1565T/C) showed milder phenotypes than expected., Data suggest a role for GPIIbIIIa integrin in caspase-3 activation induced by these platelet agonists., These data provide a mechanism for enhancement of platelet activity by alpha(IIb)beta(3) inhibitors, but also reveal a potentially important signaling pathway operating from the integrin to GPVI signaling., analysis of ITGA2B and ITGB3 mRNA splicing, expression, and structure-function relationship in Glanzmann thrombasthenia, Data show that cartilage oligomeric matrix protein (COMP) promotes cell attachment via independent mechanisms involving cell surface CD47 and alphaVbeta3 integrin and that cell attachment to COMP induces formation of fascin-stabilized actin microspikes., provide the first proof that talin binding is sufficient to activate and extend membrane-embedded integrin alphaIIbbeta3, thereby resolving numerous controversies and enabling molecular analysis of reconstructed integrin signaling., study demonstrates not only a function of integrin alphaIIbbeta3 as a noncanonical Galpha13-coupled receptor but also a new concept of Galpha13-dependent dynamic regulation of RhoA, the 807T allele of GP Ia and the PlA2 allele of GP IIIa, and specially its combination confer an additional risk for development of carotid atherosclerosis and arterial thrombosis in type 2 diabetes, Variant type Glanzmann thrombasthenia caused by homozygous p.724R>X mutation in beta3 integrin., In CAD patients receiving daily low dose of aspirin, there is a significant and independent association between the expression of GPIIIa PlA1 allele and the occurrence of persistent platelet hyperactivity detected with PFA-100, Here, the authors determined that pathogenic hantaviruses bind to quiescent platelets via a beta(3) integrin-dependent mechanism., The ITGB3 Leu33Pro amino acid substitution seems to be unrelated to the development of oxaliplatin-induced peripheral neuropathy, but it appears to be related to its severity., results presented here strongly suggest that MMP-2 interacts with alpha(IIb)beta(3) to regulate the shedding of CD40L exposed on the surfaces of activated human platelets, Results proved the importance of VEGF and integrin alphavbeta3 in the pathogenesis of AML., the interaction between Trp110 of alphaIIb and Arg261 of beta3 is critical for alphaIIbbeta3 integrity and outside-in signaling-related functions, in the presence of alphavbeta3-integrin Rac1 is not required for tumor angiogenesis, analysis of the effect of limiting extension at the alphaIIb genu on ligand binding to integrin alphaIIbbeta3, GPIIIA gene (PI a allele) polymorphism efects on the frequency of complicated coronary heart disease in patients with dyslipidemia and hypertensive disease., Study helps define the pathophysiology of two rare ITGB3 mutations giving rise to GT, and describe the first patient with a qualitative alphaIIbbeta3 deficiency with both inhibitory and partially activating amino acid substitutions on the beta3 subunit., Demonstrate associations between ischemic stroke functional outcome and 2 COX-2 variants (rs20417 and rs5275) and a GPIIIa variant (rs5918)., These results suggest that PKD1-regulated alphavbeta3 trafficking contributes to the angiogenesis process by integrating VEGF-A signaling with extracellular matrix interactions., a mutation in alphaIIbbeta3 integrin may have a role in Glanzmann thrombasthenia [case report], the Tie2/alphavbeta3 integrin association-induced integrin internalization and degradation are mechanistic consequences of endothelial Ang-2 stimulation, Frequency of glycoprotein IIIa gene variants that cause HPA-1 genotyping discrepancies., Alpha(V)beta(6), but not alpha(V)beta(3), blocked human parechovirus 1 cellular infectivity., The expression levels of integrins alpha5, beta1 and beta3 predicted overall survival and disease free survival in early stage non-small cell lung cancer patients, structure and mechanism of action of seems to depend on discrete transitions and to be more tightly coupled to the local environment than previously thought, [REVIEW] structure for the IIbbeta3 cytosolic domain heterodimer as it might exist in resting IIbbeta3 and protein interactions provide a background for understanding the pathogenesis of genetic bleeding disorder, A fragment of vitronectin containing the RGD integrin binding site showed similar binding affinity as that of full vitronectin protein to purified integrin alphavbeta3 but had diminished cell adhesion and spreading function in vivo., Cross-talk between serine/threonine protein phosphatase 2A and protein tyrosine phosphatase 1B regulates Src activation and adhesion of integrin alphaIIbbeta3 to fibrinogen., immunohistochemistry of the endometrium indicates that the use of osteopontin and alphavbeta3 integrin as targets for contraceptive approaches or understanding of the pathogenesis of infertility offer little benefit compared with histological dating, We have determined crystal structures of the alpha(IIb)beta(3) headpiece in the absence of ligand, Tyrosine phosphorylation of integrin beta3 regulates kindlin-2 binding and integrin activation., Integrin {beta}3 phosphorylation dictates its complex with the Shc phosphotyrosine-binding (PTB) domain., glycoprotein IIIa PlA1/PlA1 genotype carriers have a significantly increased risks of acute vascular ischemic events associated with a poor prognosis at 1 year., The alphaIIbbeta3 deficiency of the proband was caused by two compound ITGA2B mutations, which were first reported in Chinese Glanzmann thrombasthenia patients., These results demonstrate that HMGB1 blocks alpha(v)beta(3)-dependent recognition and uptake of apoptotic cells., two orthogonal events regulate integrin alphaIIbbeta3's interactions with fibrinogen, Data showed that EhPCP5 RGD motif is a ligand for alpha(V)beta(3) integrin-mediated adhesion on colonic cells and represents a novel mechanism to trigger an inflammatory response in the pathogenesis of intestinal amebiasis., genetic polymorphism is associated with an increased risk of cardiovascular adverse events, TNF-alpha enhances the migration of chondrosarcoma cells by increasing alphavbeta3 integrin expression through the MEK/ERK/NF-kappaB signal transduction pathway., Identification of interacting hot spots in the beta3 integrin stalk using comprehensive interface design., Leptin stimulates the migration of human prostate cancer cells via transcriptional up-regulation of alphavbeta3 integrin expression., our results collectively support the hypothesis that alphavbeta3 integrin has dual actions depending on the cell environment, and provide additional evidence on the role of integrins in pancreatic cancer, findings indicate that Glycoprotein IIIa leu33pro polymorphism is associated with early, spontaneous miscarriage., Data suggest that the GPIIIa and FcgammaRIIa platelet receptor polymorphisms do not influence S. aureus-platelet interactions in vitro or the clinical course of infective endocarditis., Streptococcus gordonii binding to the alpha(IIb)beta(3)/FcgammaRIIa integrin/ITAM signaling complex results in platelet activation that likely contributes to the thrombotic complications of infective endocarditis., Expression of integrin beta3 and its ligand tenascin-3 decrease the expression of uPA through p38MaPK in breast neoplasms., There was a significant association between a common ITGB3 haplotype and autism spectrum disorder., Role of integrin beta 3 polymorphisms in embryo implantation and placentation., case report of anterior ischemic neuropathy in Crohn's disease with homozygous C677T genetic polymorphism and GPIIIa variant, When polymorphonuclear leukocytes are recruited to tumor cells in a tumor microenvironment, alphaVbeta3 and intercellular adhesion molecule (ICAM)-1 may participate in multistep fibrin(ogen)-mediated melanoma cell adhesion within the circulation., Data show that the alphaIIb cytoplasmic domain is largely disordered, but it interacts with and influences the conformation of the beta3 cytoplasmic domain., ITGB3 is known to be expressed on the surface of astrocyte cells in the brain. It has been shown to play a role in various developmental processes, These data provide important quantitative and qualitative characteristics of alphaIIbbeta3-fibrinogen binding and unbinding that underlie the dynamics of platelet adhesion and aggregation in blood flow., The ITGB3 1565T/C polymorphism was found to be negatively, associated with RPL., the role of acidic extracellular pH in regulating activation of integrin alpha(v)beta(3)., kindlin-2 promotes integrin b1 and b3 activation., CCN3 enhances the migration of chondrosarcoma cells by increasing MMP-13 expression through the alphavbeta3/alphavbeta5 integrin receptor, FAK, PI3K, Akt, p65, and NF-kappaB signal transduction pathway., Suggest that individuals with Leu33Pro polymorphism of the GPIIIa glycoprotein may be predisposed to increased risk of atherosclerotic plaque rupture., Single nucleotide polymorphisms of integrin beta-3 gene is not associated with colorectal cancer., GPIIb/IIIa is the primary receptor set involved in platelet adhesion to adsorbed fibrinogen and serum albumin irrespective of their degree of adsorption-induced unfolding, while the GPIb-IX-V receptor complex plays an insignificant role., TLR2/+596 genotype may influence the association between ITGB3 single nucleotide polymrophisms and mold sensitization in adults with asthma., IL-8 increases integrin beta 3 expression and cell motility in human chondrosarcoma cells, these studies suggest that ITGB3 plays an important role in ROS-induced migration and invasion in colorectal cancer., alpha(v)beta(3) integrin has dual actions depending on the cell environment., A vicinal thiol-containing population of alphaIIbbeta3 provides redox sensitive sites for regulation of alphaIIbbeta3., Only the threonine 410 gets dephosphorylated, possibly in an integrin aIIbb3-dependent manner, beta3-integrin has an essential effect on tumor cell proliferation and progression, and may be a potential therapeutic target for the prevention of skeletal metastases of lung cancer., analysis of alpha(nu)beta(3) integrin expression by (64)Cu- and (68)Ga-labeled RGD conjugates, The PlA1/A2 polymorphism of the GpIIIa gene was associated with deep vein thrombosis in our Italian Behcet disease patients, but does not seem to increase the risk of DVT due to factor V Leiden or prothrombin gene G20210A mutations., Intact alphaIIbbeta3 integrin is extended after activation, We now look at the repertoire of ITGA2B and ITGB3 gene defects, reexamine the relationship between phenotype and genotype, and review integrin structure in the many variant forms., BMP-7 may exert anti-invasive actions by inhibiting TGF-beta-induced expression of integrin beta(3)., designed mutations at interface between alphaIIb-subunit thigh domain and beta3-subunit I-EGF2 domain to determine effect of this interface during integrin inside-out activation and outside-in signaling, alphanubeta3 and alphanubeta5 have roles in photon-induced hypermigration of malignant glioma cells, There was no evidence for differences in integrin alpha1, alpha4, beta1 and beta3 protein levels between the follicular and mid-luteal staged samples., Direct intracoronary bolus injection resulted in a more pronounced local inhibition of platelet function and a higher degree of GP IIb/IIIa receptor occupancy as compared to standard intravenous bolus injection., Platelet alphaIIbeta3 and alpha2beta1 levels were measured by flow cytometry in 320 acute coronary syndrome patients and 128 normal subjects and compared with MPV, platelet count, ITGA2 rs1126643, and ITGB3 rs5918 alleles., This case-control study identified 3 genes (CYP2C19, ABCB1, and ITGB3) and 2 clopidogrel-related factors (loading dose and proton pump inhibitors) that were independently associated with early stent thrombosis, we show that while wild-type kindlin-2 is capable of promoting integrin alpha2b/beta3 activation, Integrin-alphavbeta3 was upregulated on various therapy-resistant tumor cells through chronic activation of ATM/Chk2-and NFkappaB-mediated pathways, study here indicated that integrin alphaVbeta3 had lower affinity when the ADMIDAS was mutated, Studies indicate that mutations increase the activation state of alphaIIbbeta3 and interfere with megakaryocytopoiesis., the point mutation in the EGF-4 domain of beta(3) integrin is responsible for the formation of the Sec(a) platelet alloantigen and affects receptor function, Thyroid hormone is shown to induce human lung cancer cell proliferation via crosstalk between integrin alphavbeta3 and ERalpha., A mutation in the beta3 cytoplasmic tail causes variant Glanzmann thrombasthenia by abrogating transition of alphaIIb beta3 to an active state., alphaVbeta3-integrin relocalizes nectin1 to lipid rafts, independently of herpes simplex virus 1., MIF enhanced the migration of chondrosarcoma cells by increasing alphavbeta3 integrin expression through the PI3K/Akt/NF-kappaB signal transduction pathway., KSHV induction of integrin beta3 is likely to be important for Kaposi's Sarcoma tumor formation, Recurrent mutations of ITGB3 is associated with Glanzmann thrombasthenia., Platelet glycoprotein IIb/IIIa polymorphism HPA-3 b/b is associated with increased risk of ischemic stroke in patients under 60 years of age., Human neutrophil alpha-defensins induce formation of fibrinogen and thrombospondin-1 amyloid-like structures and activate platelets via glycoprotein IIb/IIIa., Disulfide bonds in EGF domains of beta3 affect structure and function of alphaIIbbeta3 and alphavbeta3 integrins in different manner., signalling through increased NEDD9 levels requires integrin beta3 signalling, which leads to elevated phosphorylation of integrin beta3, Hantaan virus infection upregulated the expression of integrin beta3 and VEGFR2., cell surface protein disulfide isomerase colocalized with beta1 and beta3 integrins after dengue virus infection, In patients with DES, who require cessation of clopidogrel before surgery, bridging with GP IIb/IIIa inhibitors appears effective in preventing adverse cardiac outcomes but may be associated with bleeding in patients undergoing cardiac surgery., The A2A2 genotype of the glycoprotein IIIa polymorphism was associated with lower risk for diabetic retinopathy in Caucasians with type 2 diabetes., identified alphaIIbbeta3 integrin as a functional galectin-1 receptor in platelets, kindlins do not promote initial talin recruitment to alphaIIbbeta3, suggesting that they co-activate integrin through a mechanism independent of recruitment, describe the generation of sCD154 mutants that lost their ability to bind CD40 or alphaIIbbeta3 and show that CD154 residues involved in its binding to CD40 or alphaIIbbeta3 are distinct from those implicated in its interaction to alpha5beta1, the role of gene polymorphism in both the thrombotic and fibrinolytic pathways in young Mexican individuals with STEAMI and suggest a synergistic effect between PIA2 and 4G allele., Disease duration of atopic myelitis is reflected in significantly higher GP IIb/IIIa values than in controls and involves the sensory system, with increased platelet aggregative function., Low concentration sclerosants activated platelets and released microparticles but inhibited platelet aggregation due to suppression of GPIIb/IIIa activation., results suggest that in some focal segmental glomerulosclerosis patients, disruption of the podocyte cytoskeleton and beta3 integrin-mediated podocyte attachment are driven by the TNFalpha pathway., show further that MYC represses transcription of both subunits of alphavbeta3 integrin, and that exogenous expression of beta3 integrin in human breast cancer cells, We propose a new inside-out activation mechanism for integrin alpha(IIb)beta(3) and by inference, all of the integrins in their native cellular environment., The talin binding to the integrin beta3 transmembrane domain(TMD) alters the topology of the TMD, resulting in integrin activation., Loss of Integrin alphaIIbbeta3 is associated with Glanzmann's thrombasthenia., Expression of ITGB3 and leukemia inhibitory factor (LIF) in the peri-implantation endometrium does not change in women with unexplained recurrent pregnancy loss., These results suggested that platelet associated anti-alphaIIbbeta3 antibodies in primary primary immune thrombocytopenia tended to recognize highly restricted regions of alphaIIb with clonality., study found in Mexican mestizo patients, the platelet GP IIIa PL(A1/A2) gene polymorphism does not lead to the sticky platelet syndrome phenotype, These studies implicate ASM as a mediator of apoptosis induced by inhibition of integrins alphavbeta3/alphavbeta5, and for the first time place c-Abl as an upstream regulator of ASM expression and activity., A similar genotype prevalence of ITGB3 was found in idiopathic sudden sensorineural hearing loss patients and controls. The PLA1/A2 polymorphism was also not associated with recovery., The findings confirm previous reports that low-avidity HPA-1a antibodies can cause neonatal alloimmune thrombocytopenia but show that the presence of such an antibody does not predict that an infant will be affected., thioridazine regulates endothelial cell functions that are relevant to angiogenesis through the suppression of the alphavbeta3/FAK/mTOR signaling pathway, Agonist stimulation, talin-1, and kindlin-3 are crucial for alpha(IIb)beta(3) activation in a human megakaryoblastic cell line, CMK., Overexpression of osteopontin, alphavbeta3 and Pim-1 associated with prognostically important clinicopathologic variables in non-small cell lung cancer., Contrary to suggestions from previous studies, fractalkine chemokine domain binds directly to integrins alphavbeta3 abd alpha4beta1 at a very high affinity., propose that alphavbeta3-integrin is considered a class of non-TLR pattern recognition receptors., alphavbeta3 integrin and nucleolin interact to regulate endothelial and glioma cell migration, RGD peptide plays an important role in the modulation of cell motility and in the perturbation of cell attachment affecting the malignant potential of breast cancer cells via binding to integrin alphavbeta3., The A2A2 genotype of the glycoprotein IIIa polymorphism was not associated with MI risk in Caucasians with type 2 diabetes., PPP1C isoforms have distinct contribution to the outside-in alphaIIbbeta3 signalling-dependent functions in HEK293 alphaIIbbeta3 cells., CtsH-mediated processing of talin might promote cancer cell progression by affecting integrin alphaVbeta3 activation and adhesion strength, These results identify a novel pathway of integrin alphaIIbbeta3 outside-in signaling and recognize the tyrosine kinase Pyk2 as a major regulator of platelet adhesion and spreading on fibrinogen., An independent impact of PL A1/A2 polymorphism on risk of stillbirth development is not be yet established but additive role of the polymorphism in combination with other thrombophilic factors should be considered., Integrins alphavbeta3 and alphavbeta5 and their ligands are expressed in distinct and heterogeneous patterns in primary and secondary central nervous system neoplasms., the PI3 kinase/Rap1 pathway is intrinsically impaired in platelets from JAK2V617F-positive essential thrombocythemia patients, resulting in diminished thrombin and thrombopoietin-mediated integrin alpha(IIb)beta(3) activation, These results suggest that alphavbeta3-IGF1 interaction, not alphavbeta3-extracellular matrix interaction, is essential for IGF signaling., Results show that mutation in integrin beta3 contributes to thrombocytopenia through gain of function mechanisms, carriage of e2/e3/e4 for polymorphism of the apoE gene, does not influence on predisposition to the longevity., The activation capacity of integrin alphaIIbbeta3 integrin was diminished in myelodysplastic syndrome platelets., The PlA2-allele of the gene encoding platelet glycoprotein-IIIa has been found to be associated with short-term cognitive dysfunction after cardiac surgery., Data indicate that EGFL7 and integrin alphavbeta3 integrin colocalized in vesicular structures in uman umbilical vein endothelial cells (HUVECs)., Data indicate that CD9 acts as scaffold and assembles a ternary JAM-A-CD9-alphavbeta3 integrin complex from which JAM-A is released upon bFGF stimulation., Results revealed that rs3809865 was significantly associated with asthma due to its effect on the binding of hsa-mir-124 to ITGB3., show that human PSG1 binds alphaIIbbeta3 and inhibits the platelet - fibrinogen interaction. Unexpectedly, however, the KGD is not critical as multiple PSG1 domains independently bind and inhibit alphaIIbbeta3 function, dRP is a novel autocrine amplifier of platelet activity, which acts on platelet redox levels and modulates integrin alphaIIbbeta3, A dual mechanism of alphaIIb-beta3 inactivation via calpain(-2) cleavage of integrin-associated proteins and via TMEM16F-dependent phospholipid scrambling with an assistant role of mPTP formation., A single disulfide bond disruption in the beta3 integrin subunit promotes thiol/disulfide exchange, in a molecular dynamics study., The study concludes that the association between PLA1/A2 polymorphism of the GPIIIa gene and the tendency to inherit migraine with aura appears significant., Integrin alphaIIbbeta3 was fully activated, independent of the morphological state of human platelets., This review focuses on the biology of integrin alphaIIbbeta3, the major membrane protein on blood platelets., results of the present study indicate likely involvement of ITGB3 and TPH2 in the pathophysiology of ASD in the Indian population., Data indicate that nuclear integrin alphav monomer in T4-exposed cells, but not integrin beta3, bound to promoters of specific genes that have important roles in cancer cells., the expression of Lewis y antigen, integrin alphav and ovarian cancer's clinical stage are both independent, drug resistance-related risk factors., Exposure of smooth muscle cells to apo(a) in migration assays induced a potent, concentration-dependent chemorepulsion that was RhoA and integrin alphaVbeta3-dependent, but transforming growth factor beta-independent., Vinblastine resistance in renal cell carcinoma can be ascribed to the overexpression of P-gp, which is regulated by the activation of the PI3K/Akt pathway and triggered by upstream CCN1-integrin avb3 interaction., Itgb3 is dispensable for normal hematopoiesis but is required for leukemogenesis., Review/Meta-analysis, A switchblade-like movement of the integrin leg is indispensable for the affinity regulation of alphaVbeta3 integrin., Interaction between CCL2 and CCR2 enhances migration of prostate cancer cells through an increase in alphavbeta3 integrin production, Kindlin-2 might promote the invasion of gastric cancer cells through enhancing proliferation and adhesion by the phosphorylation of integrin beta1 and beta3., Meta-analysis showed that ITGB3 SNPs are associated with age at onset in schizophrenia., study provides evidence that (99m)Tc-RGD-4CK is a promising agent for noninvasive determination of alphabeta3 integrin status and therapy monitoring in BAC, Results show a constitutive interaction between Src kinase and beta3 integrin through its SH3 domain and the phosphorylation of tyrosine in beta3 prevents this interaction., Studies indicate that Glanzmann thrombasthenia (GT) is caused by quantitative or qualitative deficiencies of alphaIIbbeta3, an integrin coded by the ITGA2B and ITGB3 genes., Spry4 overexpression resulted in decreased integrin beta3 protein levels in a post-transcriptional manner in part by modulating its tyrosine phosphorylation by c-Src. Spry4 knockdown increased integrin beta3 protein levels and tyrosine phosphorylation., ITGB3 and MAP4K3 are directly repressed by let-7c, altering the metastatic potential of lung cancer cells., Patients with the ACE DD genotype plus 1 or 2 unfavorable genotypes, the AT1R No-AA, the GPIIIa No-a1a1 or a combination of both, have twice higher the risk of MACE during their clinical follow-up., PA2 allele represents a risk factor for ST elevation myocardial infarction in young Mexican individuals but not for idiopathic ischemic stroke, ITGB3 expression is significantly lower in the endometrium of adenomyosis patients than in controls, GIC lines and their derived differentiated cultures expressed CD95 on the cell surface and were sensitive towards APO010-mediated cell death to a variable extent, Platelets lacking ERp57 have defective activation of the alphaIIbbeta3 integrin and platelet aggregation. The defect in aggregation was corrected by the addition of exogenous ERp57, implicating surface ERp57 in platelet aggregation., HOXA10-PCAF association impairs embryo implantation by inhibiting ITGB3 protein expression in endometrial epithelial cells., These results demonstrate that serine/threonine phosphatases, probably PP2A, regulate both inside-out and outside-in mechanisms of signal transduction and clot retraction through Platelet Glycoprotein GPIIb-IIIa Complex in human platelets., Herpes simplex virus gH/gL sufficed to elicit type I IFN and NF-kappaB activation via alphavbeta3 integrin in epithelial and neuronal cell lines., Data indicate that mutations in alphaIIbbeta3 integrins decreased ligand binding and adhesion., Our data indicate an important role for the region that links the distal calf-2 and beta-tail domains to their respective transmembrane (TM) domains in transmitting the conformational changes in the TM domains associated with inside-out activation., Direct binding of Galpha13 to integrin beta3 mediates outside-in signaling and thrombus formation., these results establish that GP IIb/IIIa and alphavbeta3 integrins are essential mediators of shear flow-induced cancer cell mechanotransduction, The mechanism of kindlin-mediated activation of integrin alphaIIbbeta3.Kindlins have little direct effect on alphaIIbbeta3 integrin monomer affinity., Gene expression analysis in CHO cells reveals that the ITGB3 P189S mutation stabilizes alphavbeta3 despite preventing alphaIIbbeta3 expression., Data show the molecular model of the complex of activated protein C (APC) with alphaVbeta3 integrin obtained by protein-protein docking approach., among patients undergoing elective percutaneous coronary intervention, the polymorphism Leu33Pro of platelet glycoprotein IIIa is associated with increased risk of periprocedural myocardial infarction only in diabetic patients, Swing-out of the beta3 hybrid domain is required for alphaIIbbeta3 integrin priming and normal cytoskeletal reorganization., [(18)F]Galacto-RGD PET/CT shows specific tracer accumulation in human atherosclerotic carotid plaques, which correlates with alphavbeta3 expression., PLA polymorphism of platelet integrin receptor, GpIIIa glycoprotein, (PLA polymorphism of the ITGB3 gene) is associated with the risk of myocardial infarction and CHD especially in young subjects., the study revealed no association between the risk of clopidogrel resistance and the presence of polymorphic variants of platelet receptor genes P2RY12 and GpIIIa., MiR-320a down-regulation mediates bladder carcinoma invasion by targeting ITGB3., Data indicate the role of vinculin in inducing the talin mediated integrin activation., It is associated with decreased ex vivo antiplatelet activity of ticagrelor in healthy Chinese male subjects., Among patients undergoing percutaneous coronary intervention for acute coronary syndromes, the polymorphism Leu33Pro of platelet glycoprotein IIIa is not associated with increased risk of periprocedural myocardial infarction., Brag2 is essential for developmental and pathological angiogenesis by promoting endothelial cell sprouting through regulation of adhesion by beta1-integrin internalization and link for the first time the process of beta1-integrin endocytosis with angiogenesis., ADAP interacts with talin and kindlin-3 to promote platelet Integrin alphaIIbbeta3 activation and stable fibrinogen binding., SNP polymorphism of GP IIIa subunit (Leu33Pro-PlA(1)/PlA(2) allele)cannot be regarded as a risk factor for coronary or carotid atherosclerosis., Integrins alphavbeta5 and alphavbeta3 both control myofibroblast differentiation by activating latent TGF-beta1, Data (including data from molecular dynamic simulations) suggest specific interactions between glycoprotein GPIIb/GPIIIa complex transmembrane/C-terminal domains and talin-1 in cell membrane environment during platelet activation., The use of LIF in combination with alphanubeta3 integrin as biomarkers appears to be superior to integrin testing alone when evaluating endometrial receptivity, primarily because of its earlier pattern of expression during the secretory phase., genetic polymorphism of the GP IIIa gene was associated with aspirin resistance in a very elderly Chinese population, Integrin alpha(v)beta expression and the resulting KRAS-RalB-NF-kappaB pathway were both necessary and sufficient for tumour initiation, anchorage independence, self-renewal and erlotinib resistance., ITGB1 rs17468 SNP and ITGB3 rs2317676 SNP were associated with an increased risk of colorectal cancer, Data show that chemokine domain of fractalkine (FKN-CD) can activate alphavbeta3 integrin in the absence of fractalkine receptor CX3CR1, but that this activation requires the direct binding of FKN-CD to alphavbeta3., The alphaII b tail sequences distal of GFFKR participate in talin-mediated inside-out alphaII b beta3 activation through its steric clashes with beta3 -bound talin, Intermolecular transmembrane domain interactions activate integrin alphaIIbbeta3., It plays a role in regulation of leukocyte migration to a site of inflammation., A novel soluble integrin beta 3 variant in the plasma of acute myeloid leukemia patients is described., Study demonstrated that versican, TGFbeta1, Col7A1 and ITGbeta3 are up-regulated in isolated Cancer stem cells., Studies sugggest that the effect of integrin alphavbeta3 in the whole process of brain function recovery merits further study., Coimmunoprecipitation studies and proximity ligation assays indicated that integrin alphavbeta3 interacts with herpes simplex virus type 2 glycoprotein H (gH)., Data suggest that endometrial levels of ITGB3 are down-regulated in women with unexplained recurrent pregnancy loss as compared to women with normal fertility during mid-secretory phase., knockdown of miR-378a increased the expression of its target proteins, vimentin, and beta3 integrin, which accelerated fibroblast migration and differentiation in vitro and enhanced wound healing in vivo., ITGB3 is downregulated 5-fold by silencing of laeverin in trophoblasts, reducing cell migration and invasion., These findings offer an explanation for the variable occupancy of the metal ion at LIMBS in alphaVbeta3 structures in the absence of ligand and provide new insights into the mechanisms of integrin regulation., diabetic retinopathy is associated with ITGA2/ITGB1 and ITGB3 PlA1/A2 polymorphisms (Meta-Analysis), The data presented here appears to demonstrate an increased risk of myocardial infarction in carriers of the PlA1/A2 polymorphism of glycoprotein IIIa, with an association that becomes stronger as age decreases., The totality of published data supports the hypothesis that carriage of the PlA2 polymorphism of GPIIIa is a risk factor for ischaemic strokes, and specifically those of cardioembolic and large vessel origin, Unlike the L33P substitution, the L33V transition would not affect the structure flexibility of the beta3 knee, and consequently the functions of alplhaIIbb3, High Integrin alpha3beta1 expression is associated with bladder cancer., Overexpression of CD98, integrin beta1, integrin beta3 and Fak is associated with the progression and liver metastases of colorectal cancer, Data show that thyroid hormones induce mitogen-activated protein kinase (MAPK) via integrin alphavbeta3 in bone marrow-derived cells from multiple myeloma (MM)., Herpesvirus 8 attachment and entry are dependent on alphaVbeta3 integrin localized to specific cell surface microdomains., Studied expression heterogeneity of ITGB3 and BCL-2 in lung adenocarcinoma tissue and adenocarcinoma cell line., In human breast cancer cells, alphavbeta3 was necessary and sufficient for Slug activation, Expression of the alphavbeta 3 integrin subunit seems to be of pathobiological and clinical relevance in patients with non-small cell lung cancer with brain metastases, 33Leu --> Pro substitution of GPIIIa does not influence the prevalence and extent of angiographically defined coronary artery disease in general population, although apparently playing a role among younger patients., Suggest a role for cyclin D1b as a possible mediator of alphavbeta3 transcription to promote breast tumor metastasis., Although our positive results are not definitive, they suggest small effect associations of the ITGB3 gene with both ASD diagnosis and symptoms of echolalia, The methylation levels in the promoter regions of OPN and integrin beta3 genes in the vascular smooth muscle cells of varicose veins are reduced and the protein expression of OPN and integrin beta3 are increased, compared with normal veins., Report novel ITGB3 mutations causing Glanzmann thrombasthenia., PAI-1 inhibits activation of VEGFR-2 by VEGF by disrupting a vitronectin-dependent proangiogenic binding interaction involving alphaVbeta3 and VEGFR-2., Conclude that tumour, rather than stromal, beta3 expression is essential and is required early for efficient spontaneous breast cancer metastasis to bone and soft tissues., Carriers of PLA2 allele compared with noncarriers had lesser grades of coronary artery stenoses but greater number of involved arteries. Carriers had more repetitive acute coronary events., ITGA3, ITGA6, ITGB3, ITGB4 and ITGB5 are associated with gastric cancer susceptibility tumor stage and lymphatic metastasis in Chinese Han population., Prevalence of alleles of polymorphic variants Leu33Pro and Leu66Arg gene ITGB3 among inhabitants of Siberia.The highest frequency of abnormal PLA2 allele (22.1%) and the PLA2/PLA2 genotype (8.8%) was observed among women, who had miscarried., suggest that the OPN-integrin alphavbeta3 axis is crucial for 5-FU resistance in oral squamous cell carcinoma, Integrin 3 modulates cell migration in an MMP2-dependent manner., Either mutation of two amino acids (D205A,D207A), or deletion of seven amino acids (Del202-208) of the Borrelia burgdorferi P66 protein significantly reduced binding ability to integrin alphavbeta3., These data identify a role of kindlin-3 phosphorylation in integrin b3 activation and provide a basis for functional differences between kindlin-3 and the two other kindlin paralogs., Anionic lipids in annular positions stabilize the alphaIIbbeta3 transmembrane complex by up to 0.50 +/- 0.02 kcal/mol relative to zwitterionic lipids in a headgroup structure-dependent manner., alpha5beta1 and alphavbeta3 each mediate actin cytoskeletal remodeling in response to stiffening or cyclic stretching of the extracellular matrix., polymorphisms in human ITGB3 may contribute to the differential responsiveness of select patients to SSRIs., This observation suggests partitioning of the activated fibrinogen bound alphaIIbbeta3 into cholesterol rich domains is not responsible for the integrin clustering observed., Osteopontin might promote a cancer stem cell-like phenotype via the alphavbeta3-NF-kappaB-HIF-1alpha pathway in hepatocellular carcinoma., Cells with beta3-betaTD_del or beta3-C560R mutations had abnormal cytoplasmic extensions on immobilized fibrinogen or Von Willebrand factor. The active conformation of alphaIIbbeta3 can induce cytoskeletal rearrangements that lead to impaired proplatelet formation., Data show that a small molecule inhibitor of the MYC transcription factor can be an effective anticancer agent when delivered using a integrin alphavbeta3 and VLA-4-targeted nanotherapy approach., beta 3 -Integrin inhibits LPS-induced autophagy in cardiomyocytes., Data indicate 114 novel missense variants in integrin alpha 2b (ITGA2B) and 68 novel missense variants in integrin beta 3 (ITGB3)., these results highlight ECO/siITGB3 nanoparticles as a promising therapeutic regimen to combat Triple-negative breast cancer, These results suggest that melatonin exerts anti-migratory and anti-invasive effects on glioma cells in response to hypoxia via reactive oxygen species-alphavbeta3 integrin-FAK/Pyk2 signaling pathways., MiR-320a inhibits metastasis in salivary Adenoid cystic carcinoma by targeting ITGB3 and may serve as a therapeutic target and prognostic marker in salivary cancers., results demonstrate that beta3 integrin expression depends on the source of the fibroblast and that its expression inhibits alphaSMA expression (and thus the myofibroblast phenotype)., IL-8 activates the PI3K/Akt pathway, which in turn activates NF-kappaB, resulting in the upregulation of integrin beta3 expression and increased invasion of estrogen receptor-negative breast cancer cells., ITGB3 expression increased with matrix rigidity. Blocking Ibeta3 reduced Gli2 and PTHrP expression. Ibeta3 co-localized with TGF-beta RII on rigid but not compliant films., Integrin alphanubeta6-mediated MMP-9 secretion facilitates pericellular matrix degradation at high cell density, promoting invasive growth of colonic neoplasms., T4, but not T3, controls integrin's outside-in signaling by phosphorylating tyrosine 759 in the beta3 subunit. ERK-mediated transcription regulation of the b3 monomer is regulated by T3 and T4which are alphavbeta3-ligands driving ovarian cancer cell proliferation ., GpIIIa 1565T/C and homozygous MTHFR 677C/T polymorphisms were higher in DVT patients compared with the control group (OR=6.65, 95% CI=3.09-14.30 and OR=4.08, 95% CI=1.35-12.38, respectively)., integrinbeta1, beta2 and beta3 are increased in patients with acute infection, which might explain the increased risk of venous thromboembolism in acute infection patients, Data show that immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by low platelet count and presence of IgG autoantibodies to platelet surface glycoproteins, such as alpha IIbbeta3 integrins., Ibrutinib causes GPVI and integrin alphaIIbbeta3 platelet signaling deficiencies that result in formation of unstable thrombi and may contribute toward bleeding., Up-regulation of integrin beta3 is associated with endometrial cancer., Activated but ligand-free integrins exist mainly in the compact conformation, whereas fibrin-bound alphaIIbbeta3 predominantly exists in a fully extended, headpiece open conformation., Data suggest that reduced ability of AnxA6-expressing cells to migrate is associated with decreased cell surface expression of integrins alphaVbeta3 and alpha5beta1., Data suggest that the ligand AGDV tetrapeptide binds to ITGB3/GPIIIa subunit and induces complete opening of headpiece of integrin alphaIIb/beta3 complex; AGDV appears to have very little contact with ITGA2B/GPIIb subunit., Our data provide evidence that ADAM23 plays a role in suppression of cancer cell progression through interaction with aVb3 integrin, and suggest that downregulation of ADAM23 in SP cells may contribute toward providing a cancer stem cell phenotype, ITGB3 c.1476G>A mutation decrease the transcription level and affect GPIIIa synthesis and CD61 antigen expression., CD61-overexpressing human umbilical cord mesenchymal stem cell, which had turned into primordial germ-like cells-like cells, could be further differentiated into male germ-like cells., Monomeric fibrin displayed a higher probability of interacting with Integrin alphaIIb beta 3 and a greater binding strength., The frequencies of the rare alleles of CCR2, ITGB3, and 3'UTR of c-fms in the Old Believers are lower than in the sample of Novosibirsk Russians, and the rare allele of DBH is more frequent,
OFFICIAL_GENE_SYMBOL ITGB3,
OMIM_DISEASE Bleeding disorder, platelet-type, 16, autosomal dominant, Glanzmann thrombasthenia, Myocardial infarction, susceptibility to, Purpura, posttransfusion, Thrombocytopenia, neonatal alloimmune,
SP_COMMENT disease:Defects in ITGB3 are a cause of Glanzmann thrombasthenia (GT) [MIM:273800]; also known as thrombasthenia of Glanzmann and Naegeli. GT is the most common inherited disease of platelets. Its inheritance is autosomal recessive. It is characterized by mucocutaneous bleeding of mild-to-moderate severity and the inability of this integrin to recognize macromolecular or synthetic peptide ligands. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb-IIIa complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the GPIIb-IIIa complex at reduced levels (5-20% controls), have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. The platelets of GT variants have normal or near normal (60-100%) expression of dysfunctional receptors., function:Integrin alpha-V/beta-3 is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIb/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions., online information:The Singapore human mutation and polymorphism database, polymorphism:Position 169 is associated with platelet-specific alloantigen HPA-4 (PEN or YUK). HPA-4A/PEN(A)/YUK(A) has Arg-169 and HPA-4B/PEN(B)/YUK(B) has Gln-169. HPA-4B is involved in neonatal alloimmune thrombocytopenia (NAIT or NATP)., polymorphism:Position 433 is associated with platelet-specific alloantigen MO. MO(-) has Pro-433 and MO(+) has Ala-433. MO(+) is involved in NAIT., polymorphism:Position 515 is associated with platelet-specific alloantigen CA/TU. CA(-)/TU(-) has Arg-515 and CA(+)/TU(+) has Gln-515. CA(+) is involved in NAIT., polymorphism:Position 59 is associated with platelet-specific alloantigen HPA-1 (ZW or PL(A)). HPA-1A/ZW(A)/PL(A1) has Leu-59 and HPA-1B/ZW(B)/PL(A2) has Pro-59., polymorphism:Position 662 is associated with platelet-specific alloantigen SR(A). SR(A)(-) has Arg-662 and SR(A)(+) has Cys-662., PTM:Phosphorylated on tyrosine residues in response to thrombin-induced platelet aggregation. Probably involved in outside-in signaling. A peptide (AA 740-762) is capable of binding GRB2 only when both Tyr-773 and Tyr-785 are phosphorylated. Phosphorylation of Thr-779 inhibits SHC binding., similarity:Belongs to the integrin beta chain family., similarity:Contains 1 VWFA domain., subunit:Heterodimer of an alpha and a beta subunit. Beta-3 associates with either alpha-IIb or alpha-V. Isoform Beta-3C interacts with FLNB. Interacts with HIV-1 Tat., tissue specificity:Isoform beta-3A and isoform beta-3C are widely expressed. Isoform beta-3A is specifically expressed in osteoblast cells; isoform beta-3C is specifically expressed in prostate and testis.,