Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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protein tyrosine kinase 2(PTK2) protein tyrosine kinase 2(PTK2) Related Genes Homo sapiens
CHROMOSOME 8,
CYTOBAND 8q24-qter,
ENSEMBL_GENE_ID ENSG00000169398,
GENERIF_SUMMARY Tyrosine phosphorylation of FAK regulates localization and downstream signaling with profound effects on cell movement., Regulation of G protein-linked guanine nucleotide exchange factors for Rho, PDZ-RhoGEF, and LARG by tyrosine phosphorylation, FAK regulates the activity of Akt/protein kinase B and GSK-3beta and the association of GSK-3beta with FAK to influence insulin-stimulated glycogen synthesis in hepatocytes., proliferative effect of fibronectin in combination with T cell lymphokines on psoriatic uninvolved basal keratinocyte progenitors may be due to abnormal in vivo integrin-driven focal adhesion kinase activity and downstream signaling., Laminin-10/11 and fibronectin differentially prevent apoptosis induced by serum removal via phosphatidylinositol 3-kinase/Akt- and MEK1/ERK-dependent pathways (Laminin 10; separate entry for Laminin 11)., comparison with FAK2 of the mechanism of tyrosine phosphorylation upon vWF interaction with glycoprotein Ib-IX-V complex, Nck-2 interacts with focal adhesion kinase (FAK), a cytoplasmic protein tyrosine kinase critically involved in the cellular control of motility, beta1 integrin regulates fibroblast viability through a PI3K/Akt/protein kinase B signaling pathway in response to a matrix-derived mechanical stimulus, Primary arrest of circulating platelets on collagen involves phosphorylation of Syk, cortactin and focal adhesion kinase, This study reports two crystal structures of the focal adhesion targeting domain of focal adhesion kinase., IGF-I protects the cells from apoptosis by blocking the activation of caspases, which may be responsible for the loss of FAK and Akt., REVIEW, Mutated focal adhesion kinase induces apoptosis in a human glioma cell line, The association of focal adhesion kinase with Wiskott-Aldrich syndrome protein is associated with cell migration in stromal cell-derived factor-1alpha-stimulated Jurkat cells, The results of this study indicate that dual inhibition of focal adhesion kinase (FAK) and epidermal growth factor receptor (EGFR) signaling pathways can cooperatively enhance apoptosis in breast cancers., Cerivastatin-induced inhibition of glioblastoma cell migration was associated with the down-regulation of tyrosine phosphorylation of FAK. FAK phosphorylation correlated well with tumor cell invasiveness., Expression of focal adhesion kinase and alpha5 and beta1 integrins in carcinomas and its clinical significance., results indicated that the mitochondrial pathway is required for ionizing radiation-induced apoptosis, and focal adhesion kinase overexpression blocks this pathway, rendering antiapoptotic states., Functional involvement of src and focal adhesion kinase in a CD99 splice variant-induced motility of human breast cancer cells, Engagement of CD44 either by its natural ligand hyaluronan or a specific antibody on a cell line induced tyrosine phosphorylation and activation of focal adhesion kinase., An altered relationship of FAK and Pyk2 was observed for different tumors and could also be important for osteosarcoma development, Results reveal a novel mechanism of FAK phosphorylation by signalling cascades involving a member of the LDL receptor family., FAK NH(2)-terminal domain fragments have roles independent of Y397, kinase, and FAT domains, R-Ras promotes focal adhesion formation by signaling to FAK and p130(Cas) through a novel mechanism that differs from but synergizes with the alpha2beta1 integrin., TGF-beta1 up-regulates expression of integrins and fibronectin, an effect that is associated with autophosphorylation/activation of FAK., Shear-induced platelet aggregation induced by 2B-rVWF binding to platelet GPIb produced pp125FAK at shear rate 4000 s-1 but not at 200 s-1, caspase-3-mediated proteolysis of FAK, an anti-apoptotic protein, is regulated by hsp72, FAK and Pyk2 function as important signaling effectors in gliomas and indicate that their differential regulation may be determining factors in the temporal development of proliferative or migrational phenotypes., This review of recent studeis provides considerable insight into the functional roles and signaling mechanisms of FAK as a positive regulator of both cell motility and cell survival., Augmented activation of FAK is an immediate signaling event required for the trans-regulation of integrin alpha L beta 2 by alpha 4 beta 1 in Jurkat T cells., Decidual beta1 integrin and FAK participate in this final step of implantation., FAK activity is regulated by low molecular weight phosphotyrosine phosphatase in human cells, FAK is activated by VEGF in human brain microvascular endothelial cells, Inhibition of FAK by antisense oligonucleotideds enhances the sensitivity of breast cancer cells to campothecin., CIB regulates platelet spreading through the regulation of FAK activation., FAK has a role in the pathology of human cancer [review], TIMP-1 activates cell survival signaling pathways involving focal adhesion kinase, phosphatidylinositol 3-kinase, and ERKs in human breast epithelial cells, both c-Src/PI3K and c-Src/Fak/Erk1/2 pathways are involved in the up-regulation of c-myc and cyclin d1 expression mediated by prolactin, FAK and Src are important survival factors, playing a role in protecting colon cancer cell lines from Adenovirus-containing FAK-CD (Ad-FAK-CD)-induced apoptosis, beta1 integrin/FAK-mediated signaling on osteoblasts could be involved in ICAM-1- and RANKL-dependent osteoclast maturation, FAK has a role in binding of soluble and surface-bound ligand to integrin alphaIIbbeta3, All ESFT cell lines expressed five- to twenty-eight-fold-increased values of FAK, . These results raise the possibility that the overexpression of c-myc and FAK are involved in the poor prognosis of ESFT., PTK2 and EIF3S3, which, respectively, encode focal adhesion kinase and the p40 subunit of the eukaryotic initiation factor 3, were probable targets within the amplification at 8q23-q24 and may be involved in progression of HCC., pp125FAK interacts with the large conductance calcium-activated hSlo potassium channel in human osteoblasts, focal adhesion kinase and src are stimulated by G alpha q and platelet activating factor receptor in vascular endothelium, The above results indicate that PKB-Ser-473 and FAK-Tyr phosphorylation stimulated by TGF-beta1 are both dependent on cell adhesion., the proteolytic degradation of FAK is temporally distinct from its tyrosine dephosphorylation, occurring when apoptotic pathways are already initiated and during a generalized destruction of signaling proteins, Extracellular pressure may increase integrin affinity and promote colon cancer adhesion via actin dependent inside-out focal adhesion kinase and Src signals. This mechanotransduced pathway may regulate metastasizing tumor cell adhesion., FAK could play an important role in hepatocellular carcinoma progression, Calcium rises locally trigger focal adhesion disassembly and enhance residency of focal adhesion kinase at focal adhesions, RhoA/Rho-kinase pathway followed by tyrosine phosphorylation of FAK and paxillin leads to ATP release and actin reorganization in vascular endothelium, Cloning and characterization of the promoter region of human focal adhesion kinase gene and analysis of nuclear factor kappa B and p53 binding sites, Results demonstrate FHL2 expression in human ovarian cancer cells, suggesting an important functional role of pp125FAK and FHL2 complex in gynecologic malignancies., FAK has a role functioning upstream of PI3K/Akt, in transducing a beta(1) integrin viability signal in collagen matrices, Activation of rho had no effect on phosphorylation of FAK., Activation of FAK and ERK1/2 by MCSP appear to involve independent mechanisms., focal adhesion kinase phosphorylation is mediated by VEGFR2 and regulated by heat shock protein 90 and Src kinase activities, Data show that squamous cell carcinoma cells escape suspension-induced, p53-mediated anoikis by forming multicellular aggregates that use fibronectin survival signals mediated by integrin alpha(v) and focal adhesion kinase., The introduction of FAK siRNA in HL-60/FAK cells sensitized them against TRAIL-induced apoptosis, confirming that overexpressed FAK downregulates procaspase-8 expression, which subsequently inhibits downstream apoptosis pathway in the HL-60/FAK cells., Overexpression and Phosphorylation of focal adhesion kinase is associated with ovarian carcinoma, The level of FAK tyrosine phosphorylation appeared to be inversely correlated with the level of the PTEN protein in human; the defect of PTEN in tumor cells could alter the phosphorylation of FAK, overexpression of FAK promoted exit from G(1) in glioblastoma cells, enhanced expression of cyclins D1 and E while reducing expression of p27(Kip1) and p21(Waf1), and enhanced the kinase activity of the cyclin D1-cyclin-dependent kinase-4 (cdk4) complex, the first FAK subdomain of the FERM domain of focal adhesion kinase has a role in its normal regulation and function in the cell, the derepression of Rb-E2F-regulated genes leads to apoptosis through inactivation of focal adhesion kinase and activation of caspase-8, Angiotensin II mediates an increase in FAK and paxillin phosphorylation and induces human umbilical vein endothelial cells migration through signal transduction pathways, RET signals through focal adhesion kinase in medullary thyroid cancer cells., identified PTK2 SNPs that displayed strong signals in joint analysis of linkage and association (unadjusted P<10(-7)) with SLE, appears to be involved in early events of integrin-mediated adhesion of circulating carcinoma cells under fluid flow in vitro and in vivo, FAK siRNA-treated cells displayed a decrease in migration when serum or EGF (epidermal growth factor) were used as chemo-attractants; results demonstrated that inhibition of FAK protein leads to alterations in cell growth and migration., FAK protein overexpression coincides with Her-2/neu overexpression and may mediate HER2 signaling via Src, resulting in PI3K/Akt activation, apoptotic is propagated by decreased phosphorylation of focal adhesion kinase (FAK), which is linked to increased phosphorylation of c-Jun N-terminal kinase (JNK) and to decreased levels of p53, integrin alpha(v) inhibition abrogates FAK phosphorylation at focal adhesion sites and diminishes MMP-2 secretion leading to reduced migration and invasion of human coronary artery smooth muscle cells, FAK can suppress p53-mediated apoptosis and inhibit transcriptional activity of p53, In the prostate carcinoma PC-3 cell model, the action of the gastrin releasing peptide (GRP) analog, bombesin (BN), on the activation of focal adhesion kinase (FAK) and invasiveness suggests that this kinase might favor metastasis, results indicate an additional mechanism for regulation of FAK activity during cell spreading and migration, involving Ser-722 phosphorylation modulated through the competing actions of GSK3beta and PP1, SOCS-3 negatively regulates cell growth and cell motility by inhibiting Janus kinase (JAK)/STAT and FAK signalings in hepatocellular carcinoma cells, We propose a model in which removal of FERM-mediated auto-inhibition is important to increase FAK catalytic activity but the translocation and clustering of this enzyme at the focal adhesions is required for maximal phosphorylation at Tyr-397., A regulatory mechanism of cell invasion was suggested whereby FAK promotes cell-surface presentation of MT1-MMP by inhibiting endophilin A2-dependent endocytosis, 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., Upregulation of focal adhesion kinase is associated with breast cancer, JSAP1.FAK complex functions cooperatively as a scaffold for the JNK signaling pathway and regulator of cell migration on FN, Data show that phosphorylation of focal adhesion kinase (FAK) at Tyr-397 is a key determinant of how FAK controls focal adhesion turnover., results suggest the possibility that therapeutic resistance to all-trans retinoic acid may be related to FAK overexpression, phosphorylation of pp125(FAK) is a late, integrin-dependent event, results suggest that platelet activation and aggregation occur in vivo in these patients, In vivo loss of FAK does not affect migration/proliferation of basal keratinocytes in the same way as it affects multipotent stem cells of the skin., FAK may act in glioblastoma as a downstream target of growth factor signaling, with integrins enhancing the impact of such signaling in the tumor microenvironment, FAK regulates integrin-dependent MMP-2 and MMP-9 expression and release by T lymphoid cells through src kinase, Data suggest that focal adhesion kinase plays a significant role in signaling pathways of a hepatocyte growth factor-responsive cell line derived from cholangiocarcinoma., FAK-induced down-modulation of RhoA activity via p190RhoGAP is a crucial step in signaling endothelial barrier restoration after increased endothelial permeability, Inhibition of FAK by SHP-2 plays a crucial role in the morphogenetic activity of Helicobacter pylori CagA., Data suggest a model in which netrin stimulates UNC5 tyrosine phosphorylation and signaling in a manner dependent on the co-receptor DCC, through the recruitment of Src and FAK kinases., While in CXCR2-expressing cells FAK phosphorylation was adhesion-dependent and was stimulated by fibronectin, in CXCR1-expressing cells FAK phosphorylation was adhesion-independent., These studies also raise the possibility that fully active forms of c-Src and Fak in breast tumors., These data suggest that FAK might differently regulate apoptosis and focal adhesion formation through site-specific, Src-dependent tyrosine phosphorylation in senescent cells., Weak expression of FAK in invasive cervical cancer is a strong independent predictor of poor patient outcome., These data demonstrate a critical role for FAK in the regulation of cyclin-dependent kinase inhibitors (CDKIs) through two independent mechanisms, FAK is up-regulated in NSCLC, and it may have a role in lung cancer progression, FAK protein abundance appears regulated at the mRNA level during gut epithelial cell motility., The technique of RNA silencing [small interfering RNA] confirmed the role of FAK in invasive prostatic cancer., Gastrin-releasing peptide upregulates ICAM-1 via FAK promotes tumor cell motility and attachment to the extracellular matrix., Enhanced expression of FAK and phospho-FAK were observed in colon cancer tissues., CAGE promotes motility of cancer cells through activation of focal adhesion kinase (FAK., FAK signaling pathways provide a link between activation of ERK1/2 by extracellular matrix proteins and mesenchymal stem cell differentiation into osteoblasts, Src and Rac1 have roles in focal adhesion kinase and ERK mitogenic signaling in epithelial cells, Our results indicate that increased FAK phosphorylation at Ser-843 represses FAK phosphorylation at Tyr-397, thus suggesting a mechanism of cross-talk between these phosphorylation sites that could regulate FAK-mediated cell shape and migration., TGF-beta1 co-ordinately and independently activates the FAK and AKT protein kinase pathways to confer an anoikis-resistant phenotype to myofibroblasts., Downregulation of either FAK or ILK expression inhibited SPARC-mediated AKT phosphorylation, and targeting both FAK and ILK attenuated AKT activation more potently than targeting either FAK or ILK alone, Src and focal adhesion kinase mediate cyclic mechanical strain-induced extracellular regulated kinase phosphorylation and proliferation of pulmonary epithelial cells., FAK was highly expressed in oral squamous cell carcinoma tissues, in contrast to none or a low expression in normal oral epithelial tissue, and the heterogeneous staining was mainly located in the cell membrane and cytoplasm, Study found that either carbachol or EGF promoted a striking ERK-dependent phosphorylation of FAK at Ser-910, but these agonists caused only slight stimulation of FAK at Tyr-397 in T84 cells., results delineate a novel force-activated inside-out Src/PI3K/FAK/Akt pathway by which cancer cells regulate their own adhesion., N-MYC induces FAK expression., Ephrin-A1 serves as a critical negative regulator in the tumorigenesis of gliomas by down-regulating EphA2 and FAK., role FAK plays in promoting cell invasion through the activation of distinct signaling pathways induced by EGF with protein MMP-9 transcription and secretion in follicular thyroid carcinoma cells, Fak/Src signaling to the PI3-K/Akt-1 and MEK/Erk pathways undergoes a differentiation state-specific uncoupling in enterocytes., These results suggest that engagement of beta1 integrins on systemic lupus erythematosus T cells could induce FAK-mediated signaling and subsequent CD40L expression and proliferation., In kidney disease, increased parathyroid hyperplasia cell growth driven by enhanced EGFR could be further aggravated through elevations in integrin beta1 and FAK expression., The expression of phosphorylated FAK was documented in all 28 cytokeratin-positive breast cancer samples., Decreased acetylglucosaminyltransferase activity due to smaall interferingRNA expression in human breast carcinoma cells resulted in attenuation of the dephosphorylation of FAK induced by epidermal growth factor., c-Abl activation by insulin, via a modification of FAK response, may play an important role in directing mitogenic versus metabolic insulin receptor signaling., STAP-2 associates with FAK and enhances its degradation, proteasome inhibitors block FAK degradation, and STAP-2 recruits an endogenous E3 ubiquitin ligase, Cbl, to FAK., Catalytic activity is required for integrin alpha5beta1-stimulated Src (Proto-Oncogene Proteins pp60(c-src)) activation., These findings provide evidence that mutations in fibronectin, induce anoikis in human squamous cell carcinoma cells by modulating integrin alpha v-mediated phosphorylation of FAK and ERK., Not cell detachment, but the proteolytic cleavage (or inhibition) of FAK is a key modulator as well as a promising indicator of apoptosis in epithelial cells under oxidative stress., FAK causes defects in spreading, reinforcement of integrin-cytoskeleton linkages and migration and at the same time could ameliorate the adhesion of metastatic cells to suboptimal surfaces., provide direct evidence of conformational regulation of FAK in living cells and novel insight into the mechanism regulating FAK conformation, The results presented here indicate that actin reorganization through FAK/PI3-K/Rac-1 activation operates in various human cancer cell systems supporting a functional role for FAK/PI-3K/Rac1/actin signaling in controlling cell motility., Increased focal Adhesion Kinase due to mutations of p53 is associated with breast and colon cancers, MAP-kinase activity necessary for TGFbeta1-stimulated mesangial cell type I collagen expression requires adhesion-dependent phosphorylation of FAK tyrosine 397., Col-IV regulates the secretion of MMP-9 via a Src and FAK dependent pathway in MCF-7 cells, These findings suggest that modified signaling mechanisms regulate cancer cell migration through an endothelial monolayer versus those involved in cell migration on or through ECM., Focal adhesion kinase as well as p130Cas and paxillin should be a crucial molecule undergoing stronger tyrosine phosphorylation in GD3-expressing melanoma cells., Structural basis for the interaction between FAK and CD4 is reported., indicate the involvement of FAK-dependent activation of extracellular signal-regulated kinase in Toll like receptor-mediated eosinophil stimulation, FAK is a pivotal signal transducer downstream of gastrin in gastric cancer., Tac-beta1 inhibits cell spreading, at least in part, by preventing the phosphorylation of FAK at Tyr-397, In human cells, FAK knockdown raised p53-p21 levels & slowed cell proliferation but did not cause apoptosis. Nuclear FAK plays a scaffolding role in facilitating cell survival through enhanced p53 degradation under stress., Concordant overexpression of p-FAK and p-ERK1/2 in extramammary Paget's disease (EMPD) is associated with the grade of malignancy of EMPD., identified the binding site of the p53 and FAK interaction and demonstrated that mutating this site and targeting the site with peptides affects p53 functioning and viability in the cells., PTPD1 is a component of a multivalent scaffold complex nucleated by FAK at specific intracellular sites, These results strongly support that Elk-1 protein is a novel binding-protein partner for FAK, a finding that significantly broadens the potential functioning of FAK and Elk-1., HEPL maintains Cas family function in localization to focal adhesions, as well as regulation of FAK activity, focal adhesion integrity, and cell spreading., simultaneous inhibition of both Focal adhesion kinase and the insulin-like growth factor-I receptor represents a potential novel therapeutic approach in human pancreatic adenocarcinoma, FAK expression is necessary for efficient phosphorylation of T-cell differentiation protein MAL following stimulation with bacterial lipopolysaccharide and protein I/II., Data show that NG2 and integrin alpha4 oppositely regulate anoikis in fibroblasts, and that NG2 and integrin alpha4 regulate FAK phosphorylation by PKCalpha-dependent and -independent pathways, respectively., Anoikis causes a down-activation of Fak, Src, Akt-1 and Erk1/2, a loss of Fak-Src association, and a sustained/enhanced activation of p38b, which is required as apoptosis/anoikis driver, focal adhesion kinase mediates caveolin-1 up-regulation during epithelial to mesenchymal transition, these data reported here support the conclusion that FAK enhances invasion of HNSCC by promoting both increased cell motility and MMP-2 production, FAK induces KLF8 expression in human ovarian cancer cells by activating the PI3K-Akt signaling pathway, leading to the activation of KLF8 promoter by Sp1, c-FLIPL promotes the motility of HeLa cells by activating FAK and ERK, and increasing MMP-9 expression., Data show that genetic upregulation of matriptase-2 reduces the aggressiveness of prostate cancer cells in vitro and in vivo and affects FAK and paxillin localisation., Focal adhesion kinase is phosphorylated in response to interferon-gamma-inducible GTPase expression., review of kinase-independent interaction of FAK with p53with focus on FAK and p53 signaling, which link signal transduction pathways, FAK is expressed by advanced-stage neuroblastoma, FAK has two nuclear export signal sequences, but only one of the signal sequences demonstrates full biological nuclear export activity., focal adhesion kinase controls the balance of adhesion types in cells, and that this is one of the determinants of whether a cancer cell can make stable matrix-degrading invadopodia., SRC-3/AIB1 is required for focal adhesion turnover and focal adhesion kinase activation., analysis of PAFR activation and pleiotropic effects on tyrosine phospho-EGFR/Src/FAK/paxillin in ovarian cancer, Focal adhesion kinase (FAK)-related non-kinase inhibits myofibroblast differentiation through differential MAPK activation in a FAK-dependent manner., These data indicate that FAK is functioning in cell migration, but fibril-forming collagen-induced FAK degradation is necessary for endothelial tube formation., Results suggest that HAb18G/CD147 enhances the invasion and metastatic potentials of human hepatoma cells via integrin alpha3beta1-mediated FAK-paxillin and FAKPI3K-Ca(2+) signal pathways., These data support the cooperative function of Pyk2 and FAK in breast cancer progression and suggest that dual inhibition of FAK and Pyk2 is an efficient therapeutic approach for targeting invasive breast cancer., The integrin beta1-focal adhesion kinase signal pathway plays a role in the invasiveness of pituitary adenomas., The interplay between FAK and ERK in androgen-independent prostate cancer cells (PC3 and DU145 cells), was investigated., Following down-regulation of MR-1, the phosphorylations of MLC2, focal adhesion kinase (FAK), and Akt were dramatically decreased, Enhanced FAK expression is associated with intestinal type gastric adenocarcinoma., FAK is essentially required in chondrocyte communication with type II collagen by regulating type II collagen expression and cell proliferation., FAK, mTOR and IGF-IR are inhibited by TAE226 in esophageal cancer cells, Overexpression of FAK is associated with HBV infection and contribution to hepatocellular carcinoma progression., The lysyl oxidase pro-peptide attenuates fibronectin-mediated activation of focal adhesion kinase and p130Cas in breast cancer cells., The expression of FRNK was enhanced and the phosphorylation of FAK was inhibited after FRNK was transiently transfected into hepatic stellate cells. FRNK also induces apoptosis of HSC., groups, analysis of FAK expression regulation and therapeutic potential [review], PGE2 greatly induced hepatocellular carcinoma cell adhesion, migration, and invasion by activating FAK/paxillin/Erk pathway., Results describe a a novel mechanism by which vitronectin receptors and focal adhesion kinase could promote cancer metastasis via ERK5 activation., Bis-phosphorylated FAK is a useful biomarker of Src kinase inhibition in vivo., FAK supports Ras- and PI3K-dependent mammary tumor initiation, maintenance, and progression to metastasis., FXR promotes endothelial cell motility through coordinated regulation of FAK and MMP-9., These results suggest that Bim, Bcl-xL, FAK and endonuclease G are involved in safingol-induced apoptosis of detached oral squamous cell carcinoma., Report expression of FAK and PTEN in bronchioloalveolar carcinoma and lung adenocarcinoma., Data demonstrate that the RhoGTPase activating protein 21 (ARHGAP21) is expressed in the nuclear and perinuclear regions of several cell lines, and interacts with the C-terminal region of focal adhesion kinase., This work demonstrates a novel role for FAK in integrin activation and the time-dependent generation of cell-extracellular matrix forces., The mRNA levels and positive rates of integrin beta1 and FAK protein were significantly higher in laryngeal carcinoma than that in the surrounding tissue and vocal cord polyp., Connective tissue growth factor enhances the migration of chondrosarcoma cells by increasing MMP-13 expression through the alphavbeta3 integrin, FAK, ERK, and NF-kappaB signal transduction pathway., phosphorylation of Y407-FAK and S732-FAK are important for FAK in modulating cell migration., AGAP2 regulates the FAK activity and the focal adhesion disassembly during cell migration., Results suggest that Fer may allow a bypass of focal adhesion kinase-related cell anchorage dependency for intracellular signal transduction in hepatocytes., Data report that endogenous Focal adhesion kinase functions upstream of cellular Src (c-Src) as a negative regulator of invadopodia formation and dynamics in breast cancer cells., Up-regulation of FAK may play an important role in the invasion of SMMC-7721 cells induced by hypoxia., c-Abl phosphorylates RACK1 at the Focal Adhesion Kinase interaction site and c-Abl kinase activity is required for interaction of Focal Adhesion Kinase with RACK1., Data show that fibroblast, endothelial and carcinoma polarity during cell migration requires FAK and is associated with a complex between FAK, p120RasGAP and p190RhoGAP (p190A), leading to p190A tyrosine phosphorylation., focal adhesion kinase expression is significantly related to subsequent hepatocellular carcinoma metastasis, The present study has focused on the expression pattern of FAK in human endometrium during the menstrual cycle., Formation of focal adhesion kinase *Grb7 complexes and Grb7 phosphorylation by FAK in an integrin-dependent manner were essential for cell migration, proliferation and anchorage-independent growth in A431 epidermal carcinoma cells., 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., EGFR-mediated sustained activation of Src intestinal epithelial cancer cells confers anoikis resistance at least in part through a consequent sustenance of Fak-Src interactions and MEK/Erk activation, Direct binding of toxin A to Src, independent of any effect on protein tyrosine phosphatase or Rho glucosylation, inhibits Src kinase activity followed by FAK/paxillin inactivation, These results suggest a novel mechanism for selective reinforcement of nascent adhesions via interplays of Nudel and FAK with paxillin to facilitate cell migration, Knockdown of focal adhesion kinase reverses colon carcinoma multicellular resistance., these data suggest a role for FAK in phosphorylation, signaling and stability of the IGF-1R., Pyk2 and FAK are downstream targets of the Rap GTPases that play a key role in regulating B cell morphology., PTEN gene might inhibit the proliferation, metastasis and invasive ability of leukemia cells via down-regulating FAK expression., Cyclic mechanical strain impairs signaling of cell migration after injury via a pathway that involves FAK-JIP3-JNK., enhanced expressions of HAb18G/CD147, MMPs, paxillin and FAK changed the distributions of cytoskeleton in the 3D reconstituted basement membrane (BM) and increased the adhesion and invasion potentials of hepatocellular carcinoma cells, ILK mediated pressure-stimulated adhesion through regulating phosphorylation of AKT and FAK., FAK, phosphatidylinositol 3-kinase, and Akt kinase are involved in the potentiating action of peptidoglycan in rheumatoid arthritis synovial fibroblasts., FAK protein positivity and overexpression correlate with important clinicopathological parameters, in breast ductal invasive carcinoma., 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., FAK-NT2 (a.a. 127-243) domain directly interacts with the N-terminal part of the IGF-1R intracellular domain., FAK has a role in human MCF-7 breast cancer cell tumorigenesis, Periostin mediates vascular smooth muscle cell migration through the integrins alphavbeta3 and alphavbeta5 and focal adhesion kinase (FAK) pathway, up-regulation of focal adhesion kinase protein may also contribute to the tumor progression of gastrointestinal stromal tumors, FAK expression regulated the cell proliferation, motility and apoptosis., STEAP4 associates with focal adhesion kinase (FAK) and regulate the activity of FAK through Y397 phosphorylation., FAK signaling plays critical roles in force-induced OPN expression in hPLFs through interaction with Rho/ROCK as upstream effectors and ERK-Elk1/ERK-c-Fos as downstream effectors., Further studies are warranted to elucidate whether FAK expression analysis is a suitable tool in stratifying patients at different risks of disease progress, and wether FAK might become a new molecular target for endometrial anticancer therapy., Mechanotransduction in these cells occurs through a FAK-Rho-ERK signaling network with extracellular signal-regulated kinase (ERK) as a bottleneck through which much of the response to mechanical stimuli is regulated., Data show that both wt and mt HOSCC cells translocate FAK into the nucleus and maintain the p53/FAK interaction post STS treatment., 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., Shockwaves enhance p38 MAPK activation, IL-2 expression, and T-cell proliferation via the release of cellular ATP and feedback mechanisms that involve P2X7 receptor activation and FAK phosphorylation., Gbeta1-mediated Fyn activation integrates FAK with AJ, preventing persistent endothelial barrier leakiness., a new role for JKAP in the modulation of FAK phosphorylation and cell motility., Results indicate that hypoxia increases migration of human umbilical cord blood mesenchymal stem cells via VEGF-mediated focal adhesion kinase phospholylation and involves the cooperative activity of the ROS, MAPK, eNOS and HIF-1alpha pathways., Downregulation of FAK-related non-kinase mediates the migratory phenotype of fibrotic lung fibroblasts., crystals of Grb2 SH2 domain-FAK belonged to space group P3(1)21, with unit-cell parameters a = b = 102.7, c = 127.6 A, alpha = beta = 90.0, gamma = 120.0 degrees., results suggest that FAK may serve as a marker of cervical lymph node metastasis of tongue cancer and that RNAi targeting FAK could serve as a potential therapeutic for the treatment of tongue cancer, Systemic delivery of plasmid DNA targeting FAK function using cationic liposome as a gene carrier represents a promising avenue for breast cancer therapy., Mda-9/syntenin acts as a molecular adaptor linking PKCalpha and FAK activation in a pathway of FN adhesion by human cancer cells., analysis of a novel role for calpain proteolysis of FAK in regulating adhesion dynamics in motile cells, FAK expression is up-regulated in hepatocellular carcinoma (HCC) and its expression is an independent prognostic factor for HCC., FAK and phosphorylation at the Y397 site plays a role in neuroblastoma cell survival, and that the FAK Y397 phosphorylation site is a potential therapeutic target for this childhood tumor., FAK may play a crucial role in mediating TGF-beta1-induced epithelial-mesenchyme transition through the activation of Akt pathway., The results suggest that Par3 directly interacts with FAK and PI3-kinase, enhancing their activities for polarized cell migration., FAK contributed to the increased adhesion in MDA-MB-231DeltaMLN64 cells., The FAK pathway plays an important role in ethanol-induced formation of a focal adhesion complex in breast cancer cells., progesterone promotes breast cancer cell movement and invasion by facilitating the formation of focal adhesion complexes via the rapid regulation of focal adhesion kinase., Oxidative stress activates FAK and accelerates cell migration in an intestinal epithelium by a PI3 kinase- and Src kinase-dependent mechanism., FAK modulation by stress hormones, especially norepinephrine and epinephrine, can contribute to tumor progression in ovarian cancer, Ovarian cancer ascites induces FAK and Akt activation in an alphavbeta5 integrin-dependent pathway, which confers protection from TRAIL-induced cell death and caspase activation., Present study aimed to evaluate by immunohistochemistry the clinical significance of FAK and Src expression in 108 patients with benign and malignant thyroid lesions., FAK is an essential downstream effector of the Raf-1/MEK1/2/ERK1/2 signaling cascade and negatively regulates the neuroendocrine and metastatic phenotype in BON carcinoid cells., Data show that the FAK and Src immunohistochemical expression was associated with certain clinicopathological parameters that are crucial for the patients' management., These data demonstrate that infection requires the binding of human papillomavirus type 16 viral particles to heparan sulfate followed by activation of focal adhesion kinase through integrin alpha 6., Studies indicate that that FAK promoter contains p53 binding sites, and that p53 inhibits FAK transcription and regulates its expression in tumor samples., PTK787 inhibits transformation of the K562 cells from G(1) phase into S phase and decreasing the expression of fak mRNA., Early malignant transformation through FAK and STAT1 networking in BRCA1 mutant ovarian epithelium., Aqueous extract of the medicinal plant Patrinia villosa Juss. induces angiogenesis via activation of focal adhesion kinase., In this study initial velocity, dead-end and product inhibition, positional isotope exchange of MgATP, solvent viscometric, and structural studies were undertaken to characterize the catalytic mechanism of FAK1., The results suggest that the elevated expression of FAK and phospho-FAK is an important feature of human glioma and may benefit us in the prediction of prognosis., ECE-1 influences prostate cancer cell invasion via both ET-1-mediated FAK phosphorylation and ET-1 independent mechanisms., This study provides the first example to explain how focal adhesion kinase is activated by receptor tyrosine kinases., Results suggest that activated Pak1 regulates colorectal cancer metastasis requiring an ERK-dependent phosphorylation of FAK at Ser-910., Estrogen regulates endometrial cell cytoskeletal remodeling and motility via focal adhesion kinase., Either focal adhesion kinase protein expression or focal adhesion kinase gene amplification was significantly correlated with cancer progression and poor prognosis in gastric cancer., Recruitment of FAK and N-WASP is necessary for cell migration and invasion induced by 17beta-estradiol in breast cancer cells., results suggest that FAK regulates the production of PGE2 via the transcriptional regulation of COX-2 mRNA in compressive stimulated PDL cells. FAK-integrin complex plays role in mechanoreception and mechanotransduction in hPDL cells., Molecular integration of the guidance information inside the axonal growth cone (GC) is still baffling. Focal adhesion kinase (FAK) interacts with a complex molecular network via multiple phosphorylation sites. [review], Studies suggest that FAK FERM domains might mediate information transfer between the cell cortex and nucleus., Plexin B1 abrogates integrin-dependent migration and activation of pp125(FAK)., GDF-9 can promote the motile and adhesive capacity of PC-3 prostate cancer cells by up-regulating expression of FAK and paxillin in a Smad dependent manner, suggesting a pro-tumourigenic role for GDF-9 in prostate cancer., Data show E-cadherin molecular dynamics in vivo following perturbation of integrin signaling by inhibiting focal adhesion kinase (FAK) and Src., These results support an important potential role of FAK-Src signalling in endometrial malignant disease progress, Results suggest that human umbilical cord blood stem cells have the potential to inhibit the angiogenesis of glioma cells through downregulation of focal adhesion kinase., p53 bound to FAK promoter in the presence of estradiol...suggesting a direct role of p53 in down regulating FAK mRNA expression., FAK is involved in the molecular circuitry of alpha4beta1 and alpha5beta1 integrins that regulate motility and invasion in macrophages., 17beta-estradiol (E(2)) regulates actin remodeling and cell movement in human umbilical vein endothelial cells through the recruitment of FAK, FAK and Akt may be dual kinase targets for prevention of cancer cell adhesion and, eventually, cancer metastasis., our results demonstrated that shRNA-mediated silencing of FAK might be a potential therapeutic approach against human malignant glioma., Quinazoline-based drugs trigger anoikis in renal cell carcinoma by targeting focal adhesion kinase survival signaling., Akt-dependent mechanisms of interference with motility/invasion of human glioblastoma cells, TNC could induce EMT-like change showing loss of intercellular adhesion and enhanced migration in breast cancer cells, associated with FAK phosphorylation by SRC., Data suggest that FAK is critically involved in osteolytic metastasis and activated in tumors, pre-osteoclasts, mature osteoclasts, and bone stromal cells, and the FAK/IGF-1R inhibitor TAE226 may be used for cancer induced bone metastasis., Enteric glia promote intestinal mucosal healing via activation of focal adhesion kinase and release of proEGF., the FAK signaling molecule plays an important role in regulating cell realignment and tenogenic differentiation of hMSCs when induced by mechanical stretch, The integrin-FAK signaling pathway is involved in the control of F. solani adhesion to human corneal epithelial cells., Dyn2 is recruited to focal adhesions by interaction with the 4.1/ezrin/radizin/moesin domain of focal adhesion kinase, which functions as an adaptor between Src and Dyn2 to facilitate Dyn2 phosphorylation., Progesterone promotes endothelial cell movement via the rapid regulation of focal adhesion kinase., Non-Smad transforming growth factor-beta signaling regulated by focal adhesion kinase binding the p85 subunit of phosphatidylinositol 3-kinase., Focal adhesion kinase (FAK) binds RET kinase via its FERM domain, priming a direct and reciprocal RET-FAK transactivation mechanism, Suggest PTPN12 and ERK5 mediate HER2-driven cell motility in ovarian cancer cells, through FAK targeting., Knockdown of AURKA inhibits the growth and invasiveness of this LSCC cell line both in vitro and in vivo. These effects may partially result from the reduced expression of FAK and MMP-2., our findings suggest that SOCS3 inactivation by promoter hypermethylation is mutually exclusive to EGFR activation in gliomas and preferentially promotes glioma cell invasion through STAT3 and FAK activation., Manipulation of EMP2 levels in endometrial cancer cells regulates the phosphorylation of FAK and Src, and promotes their distribution into lipid raft domains., the loss of ARHI expression in the majority of ovarian cancers may result in the upregulation of Stat3 and FAK activity, and thereby contribute to oncogenesis., Cortactin and focal adhesion kinase have roles in cancer risk in patients with laryngeal premalignancy, VEGF binding to NRP1 is essential for VEGF stimulation of endothelial cell migration, complex formation between NRP1 and VEGFR2, and signaling via FAK Tyr407 phosphorylation., Myocilin, a glaucoma-associated protein, promotes cell migration through activation of integrin-focal adhesion kinase-serine/threonine kinase signaling pathway., A cell penetrating peptide derived from azurin inhibits angiogenesis and tumor growth by inhibiting phosphorylation of VEGFR-2, FAK and Akt., Cortactin interacts with and stimulates the kinase activity of focal adhesion kinase upon Helicobacter pylori infection., These results demonstrate that FAK signaling is critical for FSS-induced activation of ERK and JNK, and for promotion of osteoblast differentiation and osteogenesis via its association with Grb2/Sos complex., Down-regulation of FAK is associated with autism., Pax-5 plays a key role in phenotypic transitioning during metastasis through the regulation of FAK1 activity. (Review), Suppression of E-cadherin function drives the early stages of Ras-induced squamous cell carcinoma through upregulation of FAK and Src., ECSM2 modulated bFGF-directed endothelial cell motility via the FGF receptor (FGFR)-extracellular regulated kinase (ERK)-focal adhesion kinase (FAK) pathway., The identification of this novel role of PYK2 reveals a new signaling pathway in human airway epithelial cells., Expression of focal adhesion kinase in small-cell lung carcinoma., that inhibition of SFK/FAK signaling can promote endocrine specification by limiting activation of the TGFbetaR/Smad2/3 pathway., The abnormal expression of DLC1 and p-FAK might participate in the carcinogenesis, progression, and metastasis of breast cancer., Cell surface HSP90 promotes human prostate cancer cell invasion through FAK/c-Src signaling., Isomerization of the phosphorylated PTP-PEST by PIN1 increases the interaction between PTP-PEST and FAK, which leads to the dephosphorylation of FAK Y397 and the promotion of migration, invasion, and metastasis of v-H-Ras-transformed cells., Suggest that RhoA/ROCK, cytoskeletal organization, and FAK compose a "signaling network" that senses mechanical stretching and drives mechanical stretch-induced tenogenic differentiation of mesenchymal stem cells., Paxillin enables attachment-independent tyrosine phosphorylation of focal adhesion kinase and transformation by RAS, RHAMM/HA interaction regulates fibrosarcoma cell adhesion via the activation of FAK and ERK1/2 signaling pathways, demonstrated that CCN6 induced the proliferation of lung fibroblasts by binding to integrin beta1, leading to the phosphorylation of FAK(Y397)., FAK undergoes S910 phosphorylation via PKCdelta and Src-dependent pathways that are important for cell spreading and sarcomere reorganization in cardiac hypertrophy., In malignant melanoma, CD147/basigin regulates integrin beta1 signaling via the phosphorylation of focal adhesion kinase., phosphorylation of p130Cas and suppression of Rho signaling by FAK were found to be important for FAK to induce the assembly of podosome rosettes., DLC1 forms a complex with two prooncogenic proteins, talin and the focal adhesion kinase (FAK). We identified an 8-aa sequence (residues 469-476) in DLC1 and designated it an LD-like motif, because it shares homology with the LD motifs of paxillin., analysis of cellular settings mediating Src Substrate switching between focal adhesion kinase tyrosine 861 and CUB-domain-containing protein 1 (CDCP1) tyrosine 734, Fascin may regulate functions of human hepatic stellate cells (HSCs) through the FAK-phosphoinositide 3-kinase-Akt pathway., activation of EphA2 participates in the regulation of fallopian tube cell adhesion via FAK dephosphorylation, Data indicate for the first time that miR-7 directly regulates cell invasion by targeting FAK in glioblastoma and that miR-7 could be a potential therapeutic target for glioblastoma intervention., paxillin and FAK mRNA expression levels were significantly correlated with the differentiation degree and depth of invasion of esophageal carcinoma and with lymph node metastasis, Hypoxia can induce the activation of cytoplasmic FAK, Grb2 and paxillin so as to regulate the migration, survival and proliferation of pulmonary artery smooth cells., plays a critical role in neutrophil transmigration, Abnormal expression of PTEN and FAK in patients with multiple myeloma may be associated with disease progression and extramedullary infiltration., Data show that c-Met induces FAK and Pyk2 phosphorylation in medulloblastoma cells., IL-32 binds to the extracellular domain of integrins and to intracellular proteins like paxillin and FAK, FAK promotes talin recruitment to nascent adhesions occurring independently of talin binding to beta1 integrins., Associations between muscle specific force and PTK2 single-nucleotide polymorphisms suggest that interindividual differences exist in the way force is transmitted from the muscle fibers to the tendon., Blocking the FAK signaling pathway can reduce the activity of MMP-2 and -9 in corneal epithelium treated with TNF-alpha., The authors show that FAK interacts with MAVS at the mitochondrial membrane in a virus infection-dependent manner and potentiates MAVS-mediated signaling via a kinase-independent mechanism., Dephosphorylation of FAK upon inhibition of beta integrin resulted in dissociation of a FAK/cortactin protein complex. This, in turn, downregulated JNK signaling and induced cell rounding, leading to radiosensitization., Modulation of Cdc42 signaling through FAK by receptor activation underlies changes in growth cone motility., Y11 significantly and specifically decreased FAK autophosphorylation., Integrin b1/Fak/Src-mediated regulation of cell survival and anoikis in human intestinal epithelial cells., Report safety, pharmacokinetic, and pharmacodynamic phase I dose-escalation trial of PF-00562271, an inhibitor of focal adhesion kinases, in advanced solid tumors., The complex effects of lysophosphatidic acid on calpain-mediated proteolysis of FAK and other adhesion proteins are likely to play a role in its ability to promote attachment, migration, and survival of prostate cancer cells., The FAK participates in the same signaling pathway in this breast cancer cell line., Data indicate a potential role of focal adhesion kinase (FAK) and Src signaling in mobile tongue squamous cell carcinoma (SCC), rendering their small-molecule tyrosine kinase inhibitors as possible treatment strategy in tongue cancer chemoprevention., These results implicate FAK as a central mediator of fibrogenesis, and highlight this kinase as a potential therapeutic target in fibrotic diseases., data demonstrate the regulation of the FAK promoter by Nanog, the direct binding of the proteins, the phosphorylation of Nanog by FAK, ADAM15 tail can transduce a percepted extracellular signal to enhance FAK and Src phosphorylation., Protein kinase G and focal adhesion kinase converge on Src/Akt/beta-catenin signaling module in osteoblast mechanotransduction., Results show that the cellular receptors, FAK, CD44v6, c-Met and EGFR, are biomarkers of survival and tumour progression in colorectal cancer. Increased staining for each receptor was also followed by expression elevation of at least one other marker., studies reveal new developmental and anti-inflammatory roles for kinase-inhibited FAK in limiting VCAM-1 production via nuclear localization and promotion of GATA4 turnover, Silencing FAK mRNA expression and DLC1 mRNA expression may markedly enhance caspase-3 and caspase-9 activities in ovarian cancer cells., focal adhesion kinase-Src family kinases signaling plays an important role in the cyclosporin A-induced migration and invasion of trophoblast cells, Thioredoxin reductase linked to cytoskeleton by focal adhesion kinase reverses actin S-nitrosylation and restores neutrophil beta(2) integrin function., our results support the hypothesis that FAK activity might be involved in the down-regulation of p53 expression in oral squamous cell carcinoma, We have, to our knowledge, demonstrated a previously unreported role for GSK3beta in modulating the motile and invasive behavior of melanoma cells through N-cadherin and FAK., a change in expression of genes encoding perinuclear Nesprins 1 and 2 (SYNE1, 2) was observed in response to topographic cues. SYNE1/2 expression was also altered by FAK depletion, VEGF-C promotes cervical cancer metastasis by activation of FAK protein through Flt-4/c-Src pathway., balanced redox-state is required for VEGF to facilitate reversible S-glutathionylation of LMW-PTP, FAK activation and endothelial cell migration, Overexpression of EZH2, FAK and pFAK correlates with well established pathologic risk factors and may predict a more aggressive biologic behavior in endometrial carcinoma., Disruption of the protein interaction between FAK and IGF-1R inhibits melanoma tumor growth., C. neoformans activates RhoGTPases and subsequently FAK, ezrin, and PKCalpha to promote their traversal across the HBMEC monolayer, which is the critical step for cryptococcal brain infection and development of meningitis., findings suggest that FAK expression is correlated with and upregulated by 14-3-3epsilon via activation of NFkappaB, REVIEW, REVIEW, hepatitis c virus, through FAK activation, may promote cytoskeletal reorganization and a pro-oncogenic phenotype in hepatocyte-like cells, and a fibrogenic phenotype in hepatic stellate cells., thioridazine regulates endothelial cell functions that are relevant to angiogenesis through the suppression of the alphavbeta3/FAK/mTOR signaling pathway, Higher expression and activation of Focal Adhesion Kinase is associated with myelodysplastic syndromes., Activation of FAK is necessary for maintaining epithelial barrier via regulating tight junction redistribution., Findings demonstrate that TM4SF5 directly binds to and activates FAK in an adhesion-dependent manner, to regulate cell migration and invasion in hepatocellular carcinoma., Downregulation of FAK gene expression or/and upregulation of DLC-1 gene expression can all inhibit the OVCAR-3 cell growth., FAK overexpression is a promising pathological factor to predict aggressive behavior and prognosis in patients with non-small cell lung cancer, particularly in the adenocarcinoma subtype., Data indicate that focal adhesion kinase (FAK) activation and cell migration require Src, Gi/Go, COX-2 and LOXs activities., FAK expression was positively correlated with ILK expression but negatively correlated with PTEN expression in SACC tissues. FAK and ILK expression was positively associated with advanced stage, Complexing of beta1 integrin the 70-kDa with CDCP1 fragment induced intracellular phosphorylation signaling, involving focal adhesion kinase-1 (FAK) and PI3 kinase (PI3K)-dependent Akt activation, Rap1 can induce cell adhesion and stimulate an accelerated rate of cell spreading through mechanisms that bypass the canonical FAK-Src-Paxillin signalling cascade, FAK is a critical downstream regulator of gastrin-releasing peptide receptor, which mediates tumorigenesis and metastasis in neuroblastoma., integrin-FAK pathway regulates compressive stress-induced expression of M-CSF, TNF-alpha, RANKL and OPG; suggests integrin-FAK complex acts as mechanoreceptor in PDL cells., SphK1 regulates tumor cell proliferation, apoptosis and invasion, which ultimately contributes to tumor progression and malignancy phenotype in colon cancer. FAK pathway, ICAM-1 and VCAM-1 may play critical roles in this SphK1mediated effect., N-WASP has a crucial proinvasive role in driving Arp2/3 complex-mediated actin assembly in cooperation with FAK at invasive cell edges, but WRC depletion can promote 3D cell motility., FAK knockdown and re-expression assays showed that FAK activity selectively promoted anchorage-independent ID8-IP cell survival. These results support the continued evaluation of FAK inhibitors as a promising clinical treatment for ovarian cancer., our data suggest that the dual inhibition of FAK and EGFR by using plasmid vector-based RNA interference might be a novel therapeutic approach to the treatment of human non-small-cell lung cancer ., High focal adhesion kinase expression is associated with glioma., The results for the first time demonstrate FAK-regulated TXNIP expression which is important for apoptotic, survival and oxidative stress signaling pathways in cancer cells., Tyr-397 phosphorylation, rather than kinase activity of FAK, is the key determinant of cell migration, Discovery of novel focal adhesion kinase inhibitors using a hybrid protocol of virtual screening approach based on multicomplex-based pharmacophore and molecular docking., FRNK acts as an endogenous negative regulator of lung fibrosis by repressing multiple profibrotic responses., SHP2 promotes growth factor-induced cell movement by acting, at least in part, on FAK., Our study suggests that the PGE EP1 receptor regulates FAK phosphorylation by activating the PKC/c-Src and EGFR signal pathways, which may coordinately regulate adhesion and migration in HCC, small-molecule inhibition of FAK attenuates Ewing sarcoma tumor growth in vivo, FAK signaling contributed to tumor growth and vasculogenic mimicry of gallbladder carcinomas., The loss of FAK in endothelial cells enhanced cell attachment and strengthened cell-cell contacts resulting in greater basal tension leading to formation of a tighter endothelial monolayer., LKB1 serves as a FAK repressor to stabilize focal adhesion sites., The FAK pathway mediates atrial fibrogenesis in atrial fibrillation patients with rheumatic mitral valve disease., A previously unrecognized role for the Net1A isoform in controlling FAK activation during planar cell movement., KLF8 and FAK cooperatively enrich the active MMP14 on the cell surface required for the metastatic progression of breast cancer., We report a protein expression profile in high-grade osteosarcoma associating beta5 integrin, FAK, and GSK3beta that significantly correlates with poor response to neoadjuvant chemotherapy., High FAK expression is associated with invasion and metastasis of lung squamous cell carcinoma., Data indicate that the anti-tumor effects of guggulsterone (GS) possibly involve multiple networks including inhibition of FAK, Src, and Jak/STAT signaling., proangiogenic signals converge to enhance expression and association of RACK1 and vimentin, which regulated FAK, resulting in successful endothelial sprout formation in three-dimensional collagen matrices., Induction of stem cell differentiation alters regulation of FAK and Src activities., Focal adhesion kinase mediates beta-catenin signaling in periodontal ligament cells, focal adhesion kinase and RhoA regulate membrane protrusion and invasion and are regulated by integrins, NEDD9 promotes migration and invasion in cervical carcinoma cells, probably via a positive feedback loop of tyrosine phosphorylation between NEDD9 and FAK or SRC., We have identified a novel pathway whereby FAK inhibition with VS-6063 overcomes YB-1-mediated paclitaxel resistance by an AKT-dependent pathway. These findings have implications for clinical trials aimed at targeting FAK., Phosphorylated-FAKSer732 was barely detectable during interphase while its levels strongly increased in mitotic cells upon activation of the EGFR/MEK/ERK/CDK5 axis in an integrin-independent manner., The current data support evidence that down-regulation of FAK could induce SAOS-2 apoptosis through the caspase-dependent cell death pathway. Inhibition of the kinases may be important for therapies designed to enhance the apoptosis in osteosarcoma, Somatic copy number alterations by whole-exome sequencing implicates YWHAZ and PTK2 in castration-resistant prostate cancer., The signaling pathway, FAK-integrin alpha5, was found to control proliferation of bladder smooth muscle cells in response to cyclic hydrodynamic pressure., enhanced FAK activation mediates chemoresistance in castrate-resistant prostate cancer , and identify a potential clinical niche for FAK TKIs., new role for PTPalpha in the regulation of motility of mammary epithelial cells in response to ErbB2 activation., FAK Activation Depends on Mechanical Tension with Fibronectin, but Not Collagen., 4 genes (EGFR, ERBB2, PTK2, and RAF1) with five SNPs (rs11238349, rs17172438, rs984654, rs11773818, and rs17172432) might be pivotal factors in the development of prostate cancer., FAK inhibits TCR-mediated signaling by recruiting C-terminal Src kinase to the membrane and/or receptor complex following TCR activation. In the absence of FAK, the inhibitory phosphorylation of Lck and/or Fyn is impaired., Activated hepatic stellate cells in the tumor microenvironment promote hepatocellular carcinoma cell migration and invasion via activation of FAK-MMP9 signaling., results demonstrated that p38 and ERK1/2 played crucial positive roles in adipogenesis, and FAK, RhoA/ROCK and cytoskeleton played negative roles, MG53 induces FAK ubiquitination with the aid of UBE2H during skeletal myogenesis., These results suggest a novel and unique role of the FAK-Del33 mutation in FAK/Src signaling in breast cancer with significant implications for metastatic potential., These findings suggest that tensile force activates FAK pathways in PDL cells, which down-regulate immune cytokine and up-regulate osteogenic protein., demonstrate that activation of M1 muscarinic acetylcholine receptor augments the restitution of epithelial barrier function in T84 cell monolayers after ethanol-induced epithelial injury, via ERK-dependent phosphorylation of focal adhesion kinase, MiR-34a is frequently downregulated in colorectal cancer and modulates the phosphorylation of FAK by negatively regulating VEGF., A ligand-receptor complex SCRG1/BST1 axis stimulates migratory activity of mesenchymal stem cells in a FAK/PI3K/Akt-dependent manner., The 2.8 A-resolution crystal structure of the human FERM domain was determined., These results suggest that miR-218 regulates the ability of TGFbeta to induce myofibroblast differentiation in fibroblasts via cezanne/FAK., MACC1 or combination of MACC1/FAK could serve as a novel biomarker in predicting the prognosis of patocellular carcinoma after liver transplantation ., inhibition of FAK, PYK2 and BCL-XL synergistically enhances apoptosis in ovarian clear cell carcinoma cell lines, the diminishment of crosstalk between phosphorylated FAK and ITGB4 due to the down-regulation of Gli family transcription factors might play a pivotal role for inhibiting ovarian cancer progression, Data indicate that osthole-directed migration activity involves down-regulation of matrix metalloproteinase (MMP)-13 and cell motility dependent focal adhesion kinase (FAK) in migration-prone glioma cells., Results indicate that nestin regulates the localisation and functions of FAK and integrin. Because nestin has been shown to be prevalent in a number of cancers, our observations have ramifications for the roles of nestin in malignant transformation., high phosphorylated FAK abundance was associated with improved overall survival in epithelial ovarian cancer, Inhibition of both FAK and FGFR2 signaling pathways can enhance anti-tumor and anti-angiogenic activities., Colocalisation of FAK and paxillin supports their suggested role in hormonal and mechano-sensitive signalling., Melittin inhibits EGF-induced tumor invasion by suppressing MMP-9 expression and FAK phosphorylation in breast cancer cells., Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours., Our findings establish a relationship between endothelial-FAK expression levels and the molecular sub-type of invasive breast cancer., Inhibition of host FAK reduced influenza A viruses replication., we identify p63 as a target of Ring1B to regulate Fak expression in breast cancer epithelial cells, SchA-FAK-p85 complex subsequently selectively recruited and activated Akt2, not Akt1, Suggest that merlin deficiency predicts mesothelioma sensitivity to treatment with FAK inhibitors., Authors propose a model whereby vimentin promotes FAK stabilization through VAV2-mediated Rac1 activation. This model may explain why vimentin expressing metastatic lung cancer cells are more motile and invasive., MELK promotes cell migration and invasion via the FAK/Paxillin pathway, and plays an important role in the occurrence and development of gastric cancer., FAK activity regulates beta5 integrin expression and anchorage-independent cell growth in ovarian carcinoma., The FAK expression in gastric cancers was significantly higher than that in non-malignant gastric mucosa., This retrospective analysis from 2 independent trials revealed that increased PTK2 expression is associated with improved outcomes for CLL patients treated with immunochemotherapy vs chemotherapy alone., Two genotypes of the FAK gene, rs7460 TT and rs7843014 CC, are possibly associated with lower gene expression and might favor the likelihood of reaching exceptional longevity in the Spanish population., Data suggests that the rho-associated protein kinase (ROCK)-focal adhesion kinase (p-FAK cascade plays an important role in the effect of caffeine in glioma cells., Overexpression of CD98, integrin beta1, integrin beta3 and Fak is associated with the progression and liver metastases of colorectal cancer, Phosphatidylinositol-4,5-bisphosphate and its generation in focal adhesions by the enzyme phosphatidylinositol 4-phosphate 5-kinase type Igamma are important in linking integrin signaling to FAK activation., The focal adhesion kinase (FAK) signaling pathway was shown to play a key role in the process of epithelial-mesenchymal transition induction in pancreatic cancer cells via ezrin phosphorylation., The knockdown of Notch1 in both hepatocellular carcinoma cell lines increased both the total expression of PTEN and its phosphorylated form but FAK and phospho-FAK expression was decreased following Notch1 depletion., Data indicate imidazo[1,2-a][1,3,5]triazines and their derivatives as selective focal adhesion kinase (FAK) inhibitors., inhibition of FAK in vitro and in vivo decreased self-renewal capacity, levels of Wnt3a and B-Catenin revealing a novel FAK-Wnt axis regulating DCIS stem cell activity., these findings reveal a novel role for Src/FAK pathway kinases in antineoplastic drug resistance, knockdown of FAK by small interfering RNA (siRNA) resulted in inhibition of CAF-CM induced cell invasion and migration in SCC-25, probably by reducing the production of monocyte chemoattractant protein-1 (MCP-1/CCL2), Data indicate that focal adhesion kinase (FAK) and jun-NH2-terminal kinase (JNK) are the key downstream effectors of heat-shock protein GRP78., FAK/CREB/TNNC1 has a role in mediating the effect of stromal MFAP5 on ovarian cancer metastatic potential, Data indicate that inhibition of focal adhesion kinase (FAK) in rheumatoid synovial fibroblasts impaired cellular invasion and migration., Eps8 is a crucial mediator of Src- and FAK-regulated processes., The host cell motility inhibitory action of Yersinia enterocolitica YspI comes about through its specific interaction with focal adhesion kinase, FAK, which is a fulcrum of focal adhesion complexes for controlling cellular motility., FAK signaling mediated tumor invasion in breast cancer cells, promoted by IGF-1R., Conformational dynamics of the focal adhesion targeting domain control specific functions of FAK in cells., The binding involved the 106-to-131 domain, corresponding to the dimerization domain of rabies virus phosphoprotein P and the C-terminal domain of FAK containing the proline-rich domains PRR2 and PRR3., data suggest a novel role for FAK in GPVI-dependent ROS formation and platelet activation and elucidate a proximal signaling role for FAK within the GPVI pathway., These results reveal a leukemic pathway involving FAK/Tiam1/Rac1/PAK1 and demonstrate an essential role for these signaling molecules in regulating the nuclear translocation of Stat5 in leukemogenesis., There was a concomitant decrease in the phosphorylation of focal adhesion kinase and paxillin, indicating that DPP9 knockdown or enzyme inhibition suppressed the associated adhesion signaling pathway, causing impaired cell movement., FRNK represents a novel mechanism to negatively regulate IL-4-mediated inflammation., Inhibition of GSK3beta attenuated the migration and invasion of glioblastoma cells associated with suppression focal adhesion kinase, guanine nucleotide exchange factors/Rac1 and c-Jun N-terminal kinase., Critical roles of atypical FAK signaling pathways in the regulation of non-apoptotic cell death, are reported., an increase in the phosphorylation level of PTPalphaTyr789 by its upstream activator, FAKDel33, leading to Src activation in certain breast cancer cells, which has significant implications for metastatic potential., PH11 restores TRAIL apoptotic pathway in pancreatic tumor cells through down-regulation of c-FLIP via inhibition of FAK and the phosphatidylinositol-3 kinase (PI3K)/AKT pathways., Data indicate that carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) promotes angiogenesis in gastric cancer via focal adhesion kinase FAK signaling., performed immunohistochemical staining for total and phosphorylated forms of FAK and Src, to evaluate the role of FAK and Src in the development of premalignant and malignant skin lesions, Lewis y leads to inhibition of apoptosis and enhancement of CAM-DR by activation of the FAK signaling pathway and upregulation of Bcl-2/Bcl-XL expression in ovarian cancer cell lines., Suggest that PFN1 plays a critical role in gastric carcinoma progression, and these effects are likely mediated through the integrin beta1/FAK pathway., FAK activation is required for IGF1R-mediated regulation of EMT, migration, and invasion in mesenchymal triple negative breast cancer., Upon glucose stimulation BAG3 is phosphorylated by FAK and dissociates from SNAP-25 allowing the formation of the SNARE complex, destabilization of the F-actin network and insulin release., Kaempferol-3-O-rutinoside induces the activation of RhoA and Rac1, downstream effectors of the FAK signaling pathway., High focal adhesion kinase expression is associated with colorectal carcinoma and hepatocellular carcinoma., Inactivation of the FAK signaling pathway by either genetic or pharmacologic methods significantly sensitizes both murine and human PTEN-null T-ALL cells to PI3K/AKT/mTOR inhibition when cultured in vitro on feeder layer cells or a matrix and in vivo, Data suggest that PTEN protein could be a biomarker for predicting response to focal Adhesion Kinase (FAK)-targeted therapy during clinical development., Down-regulation of ARNT promotes colorectal cancer metastasis by activating the fibronectin/integrin beta1/FAK axis., FAK and p53 coordinately control each other's expression and interact in neuroblastoma., Results demonstrate a unique role for Yes in phosphorylation of FAK and in promoting PCa metastasis. Therefore, phosphorylated FAK Y861 and increased Yes expression may be predictive markers for PCa metastasis., 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., In this review, we give an overview for FAK signaling in cancer cells as well as tumor microenvironment that provides new strategies for the invention of cancer development and malignancy, FLNb enhances invasion of cancer cells through phosphorylation of MRLC and FAK., Data show that lipocalin 2 (LCN2)-induced migration occurred through activation of the met proto-oncogene protein (Met)/focal adhesion kinase (FAK) cascade., We demonstrate for the first time that FAK is overexpressed in PanNETs and that inhibition of FAK activity induces apoptosis and inhibits PanNET proliferation., FAK expression in endometrial stromal cells from endometriosis was more sensitive to estrogen, which might contribute to the pathogenesis and progress of endometriosis., CA down-regulates the VEGFR2/Src/FAK/cdc42 axis., SPON1 promotes metastatic progression through Fak and Src dependent pathway in human osteosarcoma., FAK enhances glycolysis and decreases mitochondrial respiration and increases key glycolytic proteins. Active/tyrosine-phosphorylated FAK directly binds to PKM2 and promotes PKM2-mediated glycolysis., Novel phosphotidylinositol 4,5-bisphosphate binding sites are being reported on focal adhesion kinase., Data suggest that the binding, but not the internalization of photoreceptor outer segments (POS) confers protective effects on retinal pigment epithelium (RPE) cells through the alphavbeta5 integrin/focal adhesion kinase (FAK)/PGC-1alpha pathway., work identifies FAK as a target of p110delta PI3K that links RhoA with PTEN and establishes for the first time that PTEN is a substrate of FAK-mediated Tyr phosphorylation, FAK and PYK2 functioned redundantly to promote the Wnt/beta-catenin pathway by phosphorylating GSK3beta(Y216) to reinforce pathway output-beta-catenin accumulation and intestinal tumorigenesis., Endothelial mTORC2 regulates angiogenesis, in part by regulation of endothelial cell FAK activity, matrix adhesion, and cytoskeletal remodeling, independent of Akt/mTORC1., data suggest a novel role for CerS6/C16-ceramide as an upstream effector of the loss of focal adhesion protein and plasma membrane permeabilization, HPW-RX40 restores the anoikis sensitivity in the metastatic breast cancer cells by inhibiting integrin beta1 and subsequent FAK activation., These results suggest that ITCs could be potential agents for the prevention of C6 glioma cell migration and invasion by decreasing FAK/JNK-mediated MMP-9 expression, Data show that active active focal adhesion kinase (FAK) localizes to integrin-containing endosomes., LPS-induced increases in intestinal TJP and intestinal inflammation were regulated by TLR4-dependent activation of the FAK/MyD88/IL-1R-associated kinase 4 signaling pathway., In human colon cancer cells, Akt1 binds focal adhesion kinase via the Akt1 kinase domain independently of the pleckstrin homology domain, Results from immunohistochemical analyses in 9 benign, 19 premalignant, and 19 malignant oral tissues showed that the immunoreactivity of FAK was observed in 5 benign (56%), 19 premalignant (100%), and 18 malignant tissues (95%), Data suggest that both KLF5 (Kruppel like factor 5) and FYN (FYN proto-oncogene) are important in regulation of migration in bladder cancer cells; KLF5 up-regulates cell migration, lamellipodia formation, FYN expression, and FAK phosphorylation., Modulation of FAK and Src adhesion signaling occurs independently of adhesion complex composition., Data suggest that, in colonic/prostatic neoplasm cells, increased expression of NDRG1 decreases activating phosphorylation of FAK and paxillin; silencing/inhibition of NDRG1 results in opposite effect and inhibits neoplasm cell migration/adhesion., Collectively, our data demonstrate that DCMF induces cell migration and promotes wound healing through activation of Src/FAK, ERK, AKT, and p38 MAPK signaling., In clinical samples of hepatocellular carcinom (HCC), miR-379-5p negatively correlated with FAK, which was up-regulated in HCC., Bit1 may be an important regulator in cell growth, apoptosis, migration and invasion of esophageal squamous cell carcinoma via targeting FAK-paxillin pathway., Combining erlotinib with FAK inhibitor was also potent in vivo as evidenced by reduced tumor growth in the A549 mouse xenograft model., Increased focal adhesion kinase(FAK)activity., Our findings suggest that the targets of FAK play a key role in metastasis, CEP-37440 decreased the cell proliferation of FC-IBC02, SUM190, and KPL4 by blocking the autophosphorylation kinase activity of FAK1 (Tyr 397).,
SP_COMMENT catalytic activity:ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate., domain:The carboxy-terminal region is the site of focal adhesion targeting (FAT) sequence which mediates the localization of FAK1 to focal adhesions., domain:The first Pro-rich domain interacts with the SH3 domain of CRK-associated substrate (BCAR1) and CASL., function:Non-receptor protein-tyrosine kinase implicated in signaling pathways involved in cell motility, proliferation and apoptosis. Activated by tyrosine-phosphorylation in response to either integrin clustering induced by cell adhesion or antibody cross-linking, or via G-protein coupled receptor (GPCR) occupancy by ligands such as bombesin or lysophosphatidic acid, or via LDL receptor occupancy. Plays a potential role in oncogenic transformations resulting in increased kinase activity., PTM:Phosphorylated on 6 tyrosine residues upon activation., similarity:Belongs to the protein kinase superfamily. Tyr protein kinase family., similarity:Belongs to the protein kinase superfamily. Tyr protein kinase family. FAK subfamily., similarity:Contains 1 FERM domain., similarity:Contains 1 protein kinase domain., subcellular location:Constituent of focal adhesions., subunit:Interacts with CAS family members and with GIT1, SORBS1 and BCAR3. Interacts with RGNEF and SHB (By similarity). Interacts with TGFB1I1., tissue specificity:Expressed in all organs tested, in lymphoid cell lines, but most abundantly in brain.,