Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
The Database for Annotation, Visualization and Integrated Discovery
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DAVID Functional Annotation Table
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growth factor receptor bound protein 2(GRB2) growth factor receptor bound protein 2(GRB2) Related Genes Homo sapiens
CHROMOSOME 17,
CYTOBAND 17q24-q25,
ENSEMBL_GENE_ID ENSG00000177885,
GENERIF_SUMMARY Investigation of the GRB2, GRB7, and CSH1 genes as candidates for the Silver-Russell syndrome (SRS) on chromosome 17q., Results indicate that leptin, after binding its receptor, leads to activation of Grb2 and several pathways for signal transduction that might lead to mitogenic effects., Coordinated traffic of Grb2 and Ras during epidermal growth factor receptor endocytosis, Grb2 and Nck act cooperatively to promote actin-based motility of vaccinia virus, grb2 tyrosine phosphorylation was decreased in Couzon syndrome., results suggest a model in which hepatitis C virus NS5A interacts with Grb2 to inhibit mitogenic signaling while simultaneously promoting the PI3K-AKT cell survival pathway by interaction with p85 PI3K, mediates recruitment of the Rab5 GTPase-activating protein RN-tre in endocyosis of EGFR, p21-activated kinase 1 (PAK1) interacts with the Grb2 adapter protein to couple to growth factor signaling, Results demonstrate that p27(Kip1) can inhibit growth factor receptor-bound protein 2 function by blocking its association with the guanine nucleotide exchange factor SOS., PNRC and Grb2, by interacting with each other, can suppress nuclear receptor-mediated regulation and growth factor-mediated regulation in human breast tissue, catalase (447)Tyr-Val-Asn-Val binds Grb2 upon phosphorylation in tumor cells when stimulated with serum or ligands for integrin receptors, Results suggest that MUC20 is a novel regulator of the Met signaling cascade which has a role in suppression of the Grb2-Ras pathway., GRB2 is necessary for RET-mediated branching of MDCK cells, Peptides with very high affinity for Grb2 were rationally designed as possible antitumor agents (review), demonstrate an interaction between Grb2 and magicin, Grb2-mediated recruitment of the functional RING domain of Cbl to the EGFR is essential and sufficient to support receptor endocytosis, p52Shc couples tyrosine kinase receptors to Ras by recruiting Grb2., Src homology 2 domain of Grb2 and the tyrosine residue tyrosine606 in CD229 are required for CD229-Grb2 complex formation., Grb2, in addition to its key function in signaling through Ras, may have a negatively regulatory role on EGF-induced PLC-gamma1 activation., EGFR-induced signaling and Grb2 are essential for formation of clathrin-coated pits accommodating the EGFR, while activation of MAPK and PI3K is not required., Y(169) and Y(179) are located within two consensus sites in PLD2 that mediate an SH2 interaction with Grb2. Y(169) and Y(179) are located within two consensus sites in PLD2 that mediate an SH2 interaction with Grb2., EGFR has six binding sites for the adapter protein Grb2, and ErbB4 has five., The full-length Grb2 proteins mediate negative regulation of the intrinsic Ras guanine-nucleotide exchange activity of hSos1., Grb2 is not essential for CD28-mediated NF-kappa B activation. The interaction between the YMNM motif of CD28 and the SH2 domain is sufficient for Grb2 binding., In T cells, the SH2 domain of GRB2 binds phosphorylated tyrosines on the adaptor protein LAT and the GRB2 SH3 domains associate with the proline-rich regions of SOS1 and CBL., By lysing primary hemopoietic cells at high pH, BCR-ABL1 protein-degradative activity was inhibited & association between BCR-ABL1 protein in complexes with adaptor proteins CBL, CRKL & GRB2 in primary chronic myeloid leukaemia material was demonstrated, biophysical analysis of Grb2-SH2 domain-swapping, Grb2 Src homology-2 domain-mediated interactions have a critical role in metastatic spread of primary solid tumors and Grb2 is inhibited by C90, These results are evidence that the Sprouty2 mechanism of ERK inhibition is independent of Grb2 binding., Grb2 functions as a factor which mediates phosphorylation of AMPK at Thr172., examination of rate of association reactions between Grb2 and epidermal growth factor receptor, These results suggest that coupling of Grb2 to Gab1 mediates the hepatocyte growth factor-induced strong activation of the ERK pathway, which is required for the inhibition of HepG2 cell proliferation., tumors expressing Grb2- and Shc-recruiting Met receptors demonstrated a marked loss in Grb2-associated adaptor protein 1 (Gab1) protein levels, which was not observed in the cell lines, consistent with a post-translationally regulated process, In human uterine leiomyomas, GRB2 were also overexpressed., Neph1 but not nephrin specifically binds to adaptor protein Grb2 and tyrosine kinase Csk in a phosphorylation-dependent manner., Thus, binding to APPL1 helps localize OCRL at specific cellular sites, and disruption of this interaction may play a role in disease., in VSMCs exposed to hyperglycemia, IGF-I stimulation of Shc facilitates the transfer of Grb2 to p85 resulting in enhanced PI3K activation and AKT phosphorylation leading to enhanced cell proliferation and migration, Grb2 may have a role in tumor growth, invasiveness and metastasis, tau interactions with Src homology 3 domains of phosphatidylinositol 3-kinase, phospholipase Cgamma1, Grb2, and Src family kinases are regulated by phosphorylation, Structural basis of the differential binding of the SH3 domains of GRB2 to SOS1 are reported., These data reveal that Grb2 facilitates the association of FasL with adaptin beta, and promotes sorting of FasL to the cell surface., Results define a novel negative cross-regulation between prolactin and epidermal growth factor involving the Jak2/Stat5a and Ras/MAPK pathways through tyrosine phosphorylation of Grb2., Loss of MADD expression resulted in reduced Grb2 and Sos1/2 recruitment to the TNFR1 complex and decreased Ras and MEKK1/2 activation, SH3 domains of GrB2 adaptor protein bind to PXpsiPXR motifs within the Sos1 nucleotide exchange factor in a discriminate manner., Overexpression of Grb2 is associated with gastric cancer., Distinct binding modes of two epitopes in GAB2 that interact with the SH3C domain of GRB2 are reported., Recruitment of the cytoplasmic adaptor Grb2 to surface IgG and IgE provides antigen receptor-intrinsic costimulation to class-switched B cells., The novel platelet adapter Dok-3 and the structurally related Dok-1 are tyrosine phosphorylated in an Src kinase-independent manner downstream of alphaIIbbeta3 in human platelets, leading to an interaction with Grb2., findings support a role for growth factor receptor-bound protein 2 in the diagnostically challenging workup of classical Hodgkin lymphoma versus primary mediastinal large B-cell lymphoma, report that FGFR2 recruits Grb2 through its C-terminal SH3 domain., the beta-catenin-dependent Wnt pathway is integrated with integrin signaling through the adaptor molecule Grb2, The binding of Grb2 adaptor to its downstream partners Sos1 and Gab1 docker is under tight allosteric regulation., 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., Grb2 regulates primarily the NPM-ALK-mediated phosphorylation of SHP2 and plays a key role in ALCL cell growth., The SH2 domain of Grb2 has the potential to be used as a binding component of a probe to detect activated-RTK (receptor tyrosine kinases) and to evaluate the effect of kinase inhibitors on RTK activation., intracellular Francisella tularensis novicida triggers temporal and early activation of Ras through the SOS2/GrB2/PKCalpha/PKCbetaI quaternary complex; Ras signalling by intracellular F. tularensis is essential for intracellular proliferation in the cytosol, Apolipoprotein E, growth factor receptor-bound protein 2, Golgi SNAP receptor complex member 1, and glucosidase, beta, acid may play a neurodegenerative role in stress urinary incontinence development., Grb2 specifically localizes to degradative structures formed in Src-transformed fibroblasts and PMA-stimulated endothelial cells, but not invadopodia or podosomes formed in macrophages., Grb2 knockdown significantly inhibits proliferation and survival of BCR-ABL-expressing CD34+ cells, but not control CD34+ cells, Histidine domain-protein tyrosine phosphatase interacts with Grb2 and GrpL, In addition to two signaling-associated proteins (GIT1 and AF6), the heterogeneous nuclear ribonucleoproteins F, H1, and H2 were thus identified as novel direct binders to GRB2., To our knowledge, this is the first report of GRB2 being significantly associated with schizophrenia in a specific population., RhoU physically associates with activated EGFR in a GRB2-dependent manner; suppression of GRB2 by RNA interference abrogates the interaction of RhoU with activated EGFR., Our data reliably define context-specific and time-dependent networks that form around GRB2 after stimulation, and reveal core and growth factor-selective complexes comprising 90 proteins identified as interacting with GRB2 in HEK293T cells., The Tat/Grb2 interaction affects also viral function by inhibiting the Tat-mediated transactivation of HIV-1 LTR and viral replication in infected primary microglia., High-resolution crystal structures of Grb2-SH2 domain bound to AICD peptides reveal a unique mode of binding where the peptides assume a noncanonical conformation that is unlike other structures of AICD peptides bound to protein-tyrosine-binding domains, ACAP4 protein cooperates with Grb2 protein to orchestrate epidermal growth factor-stimulated integrin beta1 recycling in cell migration, 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., the negative loop on p38 is mediated by c-ABL phosphorylation at tyrosine 105 of the adaptor protein NCK1, while the phosphorylation at tyrosine 209 of GRB2 down-modulates ERK1/2 and JNKs signaling., T-cell antigen receptor (TCR)-mediated Erk activation requires RasGRP1, but not Grb2/Sos., multiple binding sites within Sos1 provide a physical route for Grb2 to hop in a flip-flop manner from one site to the next through facilitated diffusion, and such rapid exchange forms the basis of cooperativity driving bivalent binding of Grb2 to Sos1, Modeling and simulation of aggregation of membrane protein LAT with molecular variability in the number of binding sites for cytosolic Grb2-SOS1-Grb2, Grb2 is thereby recruited into the plexin-B1 receptor complex and, through its SH3 domain, interacts with p190 RhoGAP and mediates RhoA deactivation., Data show that bivalent binding drives the formation of the Grb2-Gab1 signaling complex in a noncooperative manner., Study describes a mechanism whereby Grb2 exerts control of FGFR2 kinase activity prior to growth factor binding., Grb2 interacts with ADAM12 and is required for ADAM12 internalization., The discovery of a negative regulatory role for Grb2 reveals that this adaptor acts as a double-edged sword in the regulation of RTK signaling., the N-terminal SH3-SH2 region of grb2 protein was in charge of binding with phosphorylated TIGIT., The results fit with a role of Grb2 in protein aggregation, achieving specificity by multivalent interactions, despite the relatively low affinity of single SH3 interactions., The Dok-3/Grb2 protein signal module attenuates Lyn kinase-dependent activation of Syk kinase in B cell antigen receptor microclusters, Although Sos1 and Gab1 recognize two non-overlapping sites within the Grb2 adaptor, allostery promotes the formation of two distinct pools of Grb2-Sos1 and Grb2-Gab1 binary signaling complexes in lieu of a composite Sos1-Grb2-Gab1 ternary complex., Grb2 exerts constitutive control over the mutually dependent activities of FGFR2 and Shp2., GRB2-mediated recruitment of THEMIS to LAT is essential for thymocyte development., EGFR interacts with Grb2 in both constitutive and EGF-dependent manners, whereas the HER3-Grb2 interaction requires the heteromerization of EGFR and HER3., suppression of Grb2 expression in HepG2 cells improved hepatic steatosis, glucose metabolism, oxidative stress, and apoptosis induced by palmitic acid incubation partly though modulating the insulin signaling pathway., A deficient lipid rafts recruitment of CD3zeta/ZAP-70/Grb2, and these proteins do not merge with GM1 within the lipid rafts., Epigenetic repression of miR-376c accelerated EGF-dependent cell migration through its target GRB2 in HuCCT1 cells., VP11/12 SFK-binding motifs recruit Lck and the activated Src family kinase then leads (directly or indirectly) to phosphorylation of additional motifs involved in recruiting p85, Grb2, and Shc., In neuronal cells, amyloid-beta protein precursor intracellular domain co-localizes with GRB2 in cell compartments., Trafficking of EGFR and Grb2 in living HeLa cells stimulated with low, physiological concentrations of EGFR ligands, was analyzed.., The combined GRB2 and GAB1 protein expression was significantly associated with aggressive tumor progression and poor prognosis in patients with hepatocellular carcinoma., SGEF interacts with Grb2., a central role for adaptor proteins p66Shc and Grb2 in the regulation of ARF1 and ARF6 activation in invasive breast cancer cells., Metastatic outcome can be dictated by the constitutive competition between Grb2 and Plcgamma1 for the phosphorylation-independent binding site on FGFR2., Recruitment of the adaptor protein Grb2 to EGFR tetramers., these results identify Grb2 and Shc as central signaling effectors of Met-driven progression of intestinal epithelial-derived cancers. Notably, they suggest that Grb2 may represent a promising target for the design of novel colorectal cancer therapies., The N-terminal SH3 domain of Grb2 specifically interacts with UVRAG, unlike the C-terminal SH3 domain. This interaction helps to understand the role of Grb2 in the autophagic maturation of vesicles., Knockdown of GRB2 suppressed LMTK3-induced CDC42 activation, blocked ITGA5 and ITGB1 expression promoted by the transcription factor serum response factor (SRF), and reduced invasive activity, GRB2 was an independent factor in prognosis of esophageal squamous cell carcinoma patients, C-SH3 of Grb2 mediates the interaction with mutant Htt and this interaction being stronger could replace Gab1, with mutant Htt becoming the preferred partner. This would have immense effect on downstream signaling events., The immunoglobulin tail tyrosine motif in the cytoplasmic segments of membrane-bound IgGs acts as the principle signal amplifier by incorporating a Grb2-Btk signaling., down-regulated molecule growth factor receptor-bound protein 2 (GRB2) was a prominent node in fourteen cell proliferation-related sub-pathways., In addition, GRB2 and UBC were found to be hub nodes in the differentially expressed subnetwork and may be used as potential biomarkers or targets for the diagnosis of bladder cancer., findings show that regions outside of the consensus PxxPxR sites drive the high affinity association of GRB2 with SH3 domain ligands, Only monomeric Grb2 is capable of upregulating MAP kinase signalling. The dimeric state is inhibitory to this process. The self-association/dissociation of Grb2 represents a switch that regulates MAP kinase activity and hence controls cancer progression., Genetic variation near GRB2 on chromosome 17q25.1 is associated with sight-threatening diabetic retinopathy., TGF-beta2 induces Grb2 to recruit PI3-K to TGF-RII that activates JNK/AP-1-signaling and augments invasiveness of Theileria-transformed macrophages., Vav associates with Grb2.,
OFFICIAL_GENE_SYMBOL GRB2,
SP_COMMENT alternative products:Additional isoforms seem to exist, domain:The SH3 domains mediate interaction with RALGPS1 and SHB., function:Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway., function:Isoform GRB3-3 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Isoform GRB3-3 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death., similarity:Belongs to the GRB2/sem-5/DRK family., similarity:Contains 1 SH2 domain., similarity:Contains 2 SH3 domains., subunit:Associates with activated Tyr-phosphorylated EGF receptors and PDGF receptors via its SH2 domain. Also associates to other cellular Tyr-phosphorylated proteins such as SIT1, IRS1, IRS4, SHC and LNK; probably via the concerted action of both its SH2 and SH3 domains. It also seems to interact with RAS in the signaling pathway leading to DNA synthesis. Binds to and translocates the guanine nucleotide exchange factors SOS. Interacts with phosphorylated TOM1L1 and MET. Interacts with the phosphorylated C-terminus of SH2B2. Interacts with phosphorylated SIT1, LAX1, LAT, LAT2 and LIME1 upon TCR and/or BCR activation. Interacts with NISCH, PTPNS1, REPS2 and the syntrophin SNTA1. Interacts with REPS1 and PIK3C2B via its SH3 domains (By similarity). Interacts with HCV NS5A via its SH3 domains. Interacts with CBL and CBLB. Interacts with JUB and CLNK (By similarity). Interacts with SHB, INPP5D/SHIP1, SKAP1 and SKAP2. Forms a complex with MUC1 and SOS1, through interaction of the SH3 domains with SOS1 and the SH2 domain with phosphorylated MUC1. Interacts with PRNP (By similarity). Interacts with RALGPS1 and with HCST. Interacts (via SH3 domain) with HEV ORF3 protein. Interacts with GAPT.,