Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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GRB2 associated binding protein 1(GAB1) GRB2 associated binding protein 1(GAB1) Related Genes Homo sapiens
CYTOBAND 4q31.21,
GENERIF_SUMMARY Unique phosphorylation mechanism of Gab1 using PI 3-kinase as an adaptor protein., comparative FISH mapping of Gab1 and Gab2 genes in human, mouse and rat, ERK negatively regulates the epidermal growth factor-mediated interaction of Gab1 and the phosphatidylinositol 3-kinase, Results indicate that Gab1 and SHP-2 promote the undifferentiated epidermal cell state by facilitating Ras/MAPK signaling., Gab1 and the Met receptor interact in a novel manner, such that the activated kinase domain of Met and the negative charge of phosphotyrosine 1349 engage the Gab1 MBD as an extended peptide ligand, Gab1 is an integrator of cell death versus cell survival signals in oxidative stress, Gab1-SHP2 interaction plays a crucial role in gp130-dependent longitudinal elongation of cardiomyoctes and cardiac hypertrophy through activation of ERK5, results reveal that Gab1 protein recruits SHP2 protein tyrosine phosphatase to dephosphorylate paxillin, SHP-2/Gab1 association is critical for linking EGFR to NF-kappaB transcriptional activity via the PI3-kinase/Akt signaling axis in glioblastoma cells, Hck-mediated phosphorylation of Gab1 and Gab2 docking proteins in IL-6-induced proliferation and survival of multiple myeloma cells., coupling of Gab1 to PI3K is important for biological responses in RET-expressing cells, extracellular signal-regulated kinases 1/2 modulate insulin action via Gab1 by targeting serine and threonine residues beside YXXM motifs, Gab1 tyrosine phosphorylation is stimulated by flow shear stress to mediate protein kinase B and endothelial nitric-oxide synthase activation in endothelial cells, RAI associates with the Grb 2-associated binder 1 (GAB 1) adapter. This association is constitutive, but, in the presence of RET oncoproteins, both RAI and GAB 1 are tyrosine-phosphorylated, and the stoichiometry of this interaction remarkably increases, Gab2 plays a pivotal role in the EGF-induced ERK activation pathway and that it can complement the function of Gab1 in the EGF signalling pathway; Gab1 and Gab2 are critical signalling threshold proteins for ERK activation by EGF., By amplifying positive interactions between survival and mitogenic pathways, GAB1 plays the critical role in cell proliferation and tumorigenesis., Gab1 appears as a primary actor in coupling VEGFR-2 to PI3K/Akt, recruited through an amplification loop involving PtdIns(3,4,5)P3 and its PH domain, Crk adaptor protein is required for the sustained phosphorylation of c-Met-docking protein Grb2-associated binder 1 (Gab1) in response to HGF, leading to the enhanced cell motility of human synovial sarcoma cell lines SYO-1, HS-SY-II, and Fuji., Bisindolylmaleimide I abolishes the FGF2-mediated association of Shp2 tyrosine phosphatase with Frs2 and Gab1., Gab1 is a novel critical regulatory component of endothelial cell migration and capillary formation with a key role in the activation of VEGF-evoked signaling pathways required for angiogenesis, HGF signaling process from Gab1 to PI3K is negatively regulated by PKC-betaII, and its loss is critical for melanoma cells to gain invasive potential., 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., moderate level of Gab1 overexpression stimulated tumor growth, the Gab1-SHP2-ERK1/2 signaling pathway comprises an inhibitory axis for IGF-I-dependent myogenic differentiation., These results underscore the non-redundant and essential roles of Gab1 and Gab2 in endothelial cells, and suggest major contributions of these proteins during in vivo angiogenesis., Gab1 couples PI3K-mediated Erythropoietin signals with the Ras/Erk pathway and plays an important role in erythropoietin receptor-mediated signal transduction involved in the proliferation and survival of erythroid cells., the phosphorylation of Gab1 by c-Src is important for hepatocyte growth factor -induced DNA synthesis, The binding of Grb2 adaptor to its downstream partners Sos1 and Gab1 docker is under tight allosteric regulation., We could not confirm a major association between Gab1 SNP (rs3805246) and the predisposition to H. pylori infection and CAG in this study populat, PECAM-1-mediated inhibition of GPVI-dependent platelet responses result from recruitment of SHP-2-p85 complexes to tyrosine-phosphorylated PECAM-1, which diminishes the association of PI3K with activatory signaling molecules Gab1 and LAT, Gab1 is a critical upstream signaling component in VEGF-induced eNOS activation and tube formation, which is dependent on protein kinase A., These data demonstrate that GAB1 is ubiquitinated by CBL and degraded by the proteasome, and plays a role in negative-feedback regulation of HGF/SF-MET signaling., Met signals through a cortactin-Gab1 scaffold complex, to mediate invadopodia., Data show that bivalent binding drives the formation of the Grb2-Gab1 signaling complex in a noncooperative manner., that aberrant Gab1 signaling can directly contribute to breast cancer progression, and that negative feedback sites in docking proteins can be targeted by oncogenic mutations., these data underscore the critical roles of Gab1 and Gab2 in IL-22-mediated HaCaT cell proliferation, migration, and differentiation., GAB1 plays an important role as part of the mechanism of by which EGFR induces induced activation of the MAPK and AKT pathway., an anti-apoptotic role of caspase-cleaved GAB1 in HGF/SF-MET signaling., 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., the acquired substrate preference for GAB1 is critical for the ERBB2 mutant-induced oncogenesis., expression of Gab1, VEGFR-2, and MMP-9 are significantly related to the malignant biological behavior of hilar cholangiocarcinoma, Gab1 as major target in linoleic acid-induced enhancement of tumorigenesis., The combined GRB2 and GAB1 protein expression was significantly associated with aggressive tumor progression and poor prognosis in patients with hepatocellular carcinoma., miR-150 can influence the relative expression of GAB1 and FOXP1 and the signaling potential of the B-cell receptor, Gab1 is an essential component of NRG1-type III signaling during peripheral nerve development., Upregulations of Gab1 and Gab2 proteins associate with tumor progression of human gliomas., 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., Galphai1/3 proteins lie downstream of KGFR, but upstream of Gab1-mediated activation of PI3K-AKT-mTORC1 signaling., Endometrial GAB1 protein and mRNA expression are reduced in women with PCOS, suggesting that the endometrium of PCOS women have a defect in insulin signaling due to GAB1 down-regulation., This study suggests potential effects of SNPs of Gab1 on the onset and susceptibility of biliary tract cancer., Studied the pleckstrin homology (PH) domain of GAB1 for cancer treatment. Using homology models we derived, high-throughput virtual screening of five million compounds resulted in five hits which exhibited strong binding affinities to GAB1 PH domain., Results suggest that Gab1 is an essential regulator of the EGF-mediated mTORC pathways and may potentially be used as a biomarker for urothelial carcinoma, EGFR-activated Src family kinases maintain GAB1-SHP2 complexes distal from EGFR., Data demonstrate that miR-409-3p is a metastatic suppressor, and post-transcriptional inhibition of the oncoprotein GAB1 is one of its mechanisms of action., We found that expression of Gab1, VEGFR-2, and MMP-9 was highly and positively correlated with each other and with lymph node metastasis and TNM stage in intrahepatic cholangiocarcinoma tissues, Gab1 protein was upregulated in cyanotic compared to acyanotic hearts suggesting that Gab1 upregulation is a component of the survival program initiated by hypoxia in cyanotic children, CVB3 targets host GAB1 to generate a GAB1-N1-174 fragment that enhances viral infectivity, at least in part, via activation of the ERK pathway,
SP_COMMENT function:Probably involved in EGF and insulin receptor signaling., PTM:Phosphorylated on tyrosine residue(s) by the epidermal growth factor receptor (EGFR) and the insulin receptor (INSR). Tyrosine phosphorylation of GAB1 mediates interaction with several proteins that contain SH2 domains., similarity:Belongs to the GAB family., similarity:Contains 1 PH domain., subunit:Interacts with GRB2 and with other SH2-containing proteins. Interacts with phosphorylated LAT2.,