GAB1

Summary

Gene Symbol: GAB1
Description: GRB2 associated binding protein 1
Alias: GRB2-associated-binding protein 1, GRB2-associated binder 1, growth factor receptor bound protein 2-associated protein 1
Species: human
Products:     GAB1

Top Publications

  1. Ingham R, Santos L, Dang Lawson M, Holgado Madruga M, Dudek P, Maroun C, et al. The Gab1 docking protein links the b cell antigen receptor to the phosphatidylinositol 3-kinase/Akt signaling pathway and to the SHP2 tyrosine phosphatase. J Biol Chem. 2001;276:12257-65 pubmed
    B cell antigen receptor (BCR) signaling causes tyrosine phosphorylation of the Gab1 docking protein. This allows phosphatidylinositol 3-kinase (PI3K) and the SHP2 tyrosine phosphatase to bind to Gab1...
  2. Cunnick J, Mei L, Doupnik C, Wu J. Phosphotyrosines 627 and 659 of Gab1 constitute a bisphosphoryl tyrosine-based activation motif (BTAM) conferring binding and activation of SHP2. J Biol Chem. 2001;276:24380-7 pubmed
    A major Grb2-associated binder-1 (Gab1) binding partner in epidermal growth factor (EGF)-stimulated cells is protein-tyrosine phosphatase (PTPase) SHP2, which contains tandem SH2 domains...
  3. Hoeben A, Martin D, Clement P, Cools J, Gutkind J. Role of GRB2-associated binder 1 in epidermal growth factor receptor-induced signaling in head and neck squamous cell carcinoma. Int J Cancer. 2013;132:1042-50 pubmed publisher
    ..We hypothesized that GAB1 may amplify EGFR-induced signaling in HNSCCs and therefore could play a role in the reduced sensitivity of HNSCC to ..
  4. Rodrigues G, Falasca M, Zhang Z, Ong S, Schlessinger J. A novel positive feedback loop mediated by the docking protein Gab1 and phosphatidylinositol 3-kinase in epidermal growth factor receptor signaling. Mol Cell Biol. 2000;20:1448-59 pubmed
    The Gab1 protein is tyrosine phosphorylated in response to various growth factors and serves as a docking protein that recruits a number of downstream signaling proteins, including phosphatidylinositol 3-kinase (PI-3 kinase)...
  5. Chan P, Sudhakar J, Lai C, Chen H. Differential phosphorylation of the docking protein Gab1 by c-Src and the hepatocyte growth factor receptor regulates different aspects of cell functions. Oncogene. 2010;29:698-710 pubmed publisher
    The docking protein Grb2-associated binder1 (Gab1) has a central role in the integration of the growth-factor signaling...
  6. Schaeper U, Gehring N, Fuchs K, Sachs M, Kempkes B, Birchmeier W. Coupling of Gab1 to c-Met, Grb2, and Shp2 mediates biological responses. J Cell Biol. 2000;149:1419-32 pubmed
    b>Gab1 is a substrate of the receptor tyrosine kinase c-Met and involved in c-Met-specific branching morphogenesis...
  7. Koyama T, Nakaoka Y, Fujio Y, Hirota H, Nishida K, Sugiyama S, et al. Interaction of scaffolding adaptor protein Gab1 with tyrosine phosphatase SHP2 negatively regulates IGF-I-dependent myogenic differentiation via the ERK1/2 signaling pathway. J Biol Chem. 2008;283:24234-44 pubmed publisher
    Grb2-associated binder 1 (Gab1) coordinates various receptor tyrosine kinase signaling pathways. Although skeletal muscle differentiation is regulated by some growth factors, it remains elusive whether Gab1 coordinates myogenic signals...
  8. Holgado Madruga M, Moscatello D, Emlet D, Dieterich R, Wong A. Grb2-associated binder-1 mediates phosphatidylinositol 3-kinase activation and the promotion of cell survival by nerve growth factor. Proc Natl Acad Sci U S A. 1997;94:12419-24 pubmed
    ..have found that the addition of NGF to PC-12 cells resulted in the phosphorylation of the Grb2-associated binder-1 (Gab1) docking protein and induced the association of several SH2 domain-containing proteins, including PI 3-kinase...
  9. Oka M, Kikkawa U, Nishigori C. Protein kinase C-betaII represses hepatocyte growth factor-induced invasion by preventing the association of adapter protein Gab1 and phosphatidylinositol 3-kinase in melanoma cells. J Invest Dermatol. 2008;128:188-95 pubmed
    ..The electrophoretic mobility of Gab1, the scaffolding adapter protein that couples activated c-Met and PI3K, was slower in the melanocytes than that in ..

More Information

Publications94

  1. Ingham R, Holgado Madruga M, Siu C, Wong A, Gold M. The Gab1 protein is a docking site for multiple proteins involved in signaling by the B cell antigen receptor. J Biol Chem. 1998;273:30630-7 pubmed
    b>Gab1 is a member of the docking/scaffolding protein family which includes IRS-1, IRS-2, c-Cbl, p130(cas), and p62(dok)...
  2. Nishida K, Yoshida Y, Itoh M, Fukada T, Ohtani T, Shirogane T, et al. Gab-family adapter proteins act downstream of cytokine and growth factor receptors and T- and B-cell antigen receptors. Blood. 1999;93:1809-16 pubmed
    We previously found that the adapter protein Gab1 (110 kD) is tyrosine-phosphorylated and forms a complex with SHP-2 and PI-3 kinase upon stimulation through either the interleukin-3 receptor (IL-3R) or gp130, the common receptor subunit ..
  3. Holgado Madruga M, Wong A. Gab1 is an integrator of cell death versus cell survival signals in oxidative stress. Mol Cell Biol. 2003;23:4471-84 pubmed
    Upon the addition of different growth factors and cytokines, the Gab1 docking protein is tyrosine phosphorylated and in turn activates different signaling pathways...
  4. McDonald C, Bhat V, Mikles D, Deegan B, Seldeen K, Farooq A. Bivalent binding drives the formation of the Grb2-Gab1 signaling complex in a noncooperative manner. FEBS J. 2012;279:2156-73 pubmed publisher
    ..techniques, we show that, whereas Grb2 exists in a monomer-dimer equilibrium, the proline-rich (PR) domain of Gab1 is a monomer in solution...
  5. Kondo A, Hirayama N, Sugito Y, Shono M, Tanaka T, Kitamura N. Coupling of Grb2 to Gab1 mediates hepatocyte growth factor-induced high intensity ERK signal required for inhibition of HepG2 hepatoma cell proliferation. J Biol Chem. 2008;283:1428-36 pubmed
    ..Moreover, the mutant receptor did not induce tyrosine phosphorylation of the docking protein Gab1. Knockdown of Gab1 using siRNA suppressed the HGF-induced strong activation of ERK and inhibition of HepG2 cell ..
  6. Nguyen L, Holgado Madruga M, Maroun C, Fixman E, Kamikura D, Fournier T, et al. Association of the multisubstrate docking protein Gab1 with the hepatocyte growth factor receptor requires a functional Grb2 binding site involving tyrosine 1356. J Biol Chem. 1997;272:20811-9 pubmed
    ..following stimulation of epithelial cells and that one of these is the Grb2-associated binding protein Gab1, a possible insulin receptor substrate-1-like signal transducer...
  7. Holgado Madruga M, Emlet D, Moscatello D, Godwin A, Wong A. A Grb2-associated docking protein in EGF- and insulin-receptor signalling. Nature. 1996;379:560-4 pubmed
    ..Here we use recombinant Grb2 to isolate a complementary DNA called Gab1 (for Grb2-associated binder-1)...
  8. Dance M, Montagner A, Yart A, Masri B, Audigier Y, Perret B, et al. The adaptor protein Gab1 couples the stimulation of vascular endothelial growth factor receptor-2 to the activation of phosphoinositide 3-kinase. J Biol Chem. 2006;281:23285-95 pubmed
    ..We observed that the Grb2-bound adapter Gab1 is tyrosine-phosphorylated and relocated to membrane fractions upon VEGF stimulation of endothelial cells...
  9. Fixman E, Holgado Madruga M, Nguyen L, Kamikura D, Fournier T, Wong A, et al. Efficient cellular transformation by the Met oncoprotein requires a functional Grb2 binding site and correlates with phosphorylation of the Grb2-associated proteins, Cbl and Gab1. J Biol Chem. 1997;272:20167-72 pubmed
    ..We show here that the 110-kDa Tpr-Met substrate corresponds to the recently identified Grb2-associated protein, Gab1. Moreover, we show that tyrosine phosphorylation of the Cbl protooncogene product as well as Gab1 required Tyr489 ..
  10. Sachs M, Brohmann H, Zechner D, Muller T, Hülsken J, Walther I, et al. Essential role of Gab1 for signaling by the c-Met receptor in vivo. J Cell Biol. 2000;150:1375-84 pubmed
    The docking protein Gab1 binds phosphorylated c-Met receptor tyrosine kinase directly and mediates signals of c-Met in cell culture. Gab1 is phosphorylated by c-Met and by other receptor and nonreceptor tyrosine kinases...
  11. Laramée M, Chabot C, Cloutier M, Stenne R, Holgado Madruga M, Wong A, et al. The scaffolding adapter Gab1 mediates vascular endothelial growth factor signaling and is required for endothelial cell migration and capillary formation. J Biol Chem. 2007;282:7758-69 pubmed
    ..We have identified the Gab1 adapter as a novel tyrosine-phosphorylated protein in VEGF-stimulated cells...
  12. Sakkab D, Lewitzky M, Posern G, Schaeper U, Sachs M, Birchmeier W, et al. Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL. J Biol Chem. 2000;275:10772-8 pubmed
    ..Upon activation, the HGF-receptor c-Met binds and phosphorylates the multisite docking protein Gab1. Besides binding motifs for phosphatidylinositol 3-kinase and Grb2, Gab 1 contains multiple Tyr-X-X-Pro (YXXP) ..
  13. Yu C, Liu Z, Cantley L. ERK negatively regulates the epidermal growth factor-mediated interaction of Gab1 and the phosphatidylinositol 3-kinase. J Biol Chem. 2002;277:19382-8 pubmed
    ..the ability of epidermal growth factor (EGF)-stimulated ERK activation to regulate Grb2-associated binder-1 (Gab1)/phosphatidylinositol 3-kinase (PI3K) interactions...
  14. Rocchi S, Tartare Deckert S, Murdaca J, Holgado Madruga M, Wong A, Van Obberghen E. Determination of Gab1 (Grb2-associated binder-1) interaction with insulin receptor-signaling molecules. Mol Endocrinol. 1998;12:914-23 pubmed
    The newly identified insulin receptor (IR) substrate, Gab1 [growth factor receptor bound 2 (Grb2)-associated binder-1] is rapidly phosphorylated on several tyrosine residues by the activated IR...
  15. Seiden Long I, Navab R, Shih W, Li M, Chow J, Zhu C, et al. Gab1 but not Grb2 mediates tumor progression in Met overexpressing colorectal cancer cells. Carcinogenesis. 2008;29:647-55 pubmed publisher
    ..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...
  16. Lock L, Frigault M, Saucier C, Park M. Grb2-independent recruitment of Gab1 requires the C-terminal lobe and structural integrity of the Met receptor kinase domain. J Biol Chem. 2003;278:30083-90 pubmed
    The Gab1 docking protein forms a platform for the assembly of a multiprotein signaling complex downstream from receptor tyrosine kinases. In general, recruitment of Gab1 occurs indirectly, via the adapter protein Grb2...
  17. Gual P, Giordano S, Williams T, Rocchi S, Van Obberghen E, Comoglio P. Sustained recruitment of phospholipase C-gamma to Gab1 is required for HGF-induced branching tubulogenesis. Oncogene. 2000;19:1509-18 pubmed
    ..activates PI3 kinase, Ras and STAT signalling pathways and phosphorylates the adaptator GRB2 Associated Binder-1 (Gab1). Gab1 is also phosphorylated in response to Epidermal Growth Factor (EGF) but is unable to induce tubule formation...
  18. Lehr S, Kotzka J, Herkner A, Klein E, Siethoff C, Knebel B, et al. Identification of tyrosine phosphorylation sites in human Gab-1 protein by EGF receptor kinase in vitro. Biochemistry. 1999;38:151-9 pubmed
    ..These results demonstrate that hGab-1 is a high-affinity substrate for the EGFR and the major tyrosine phosphorylation site Y657 in the C terminus is a specific binding site for the tyrosine phosphatase Syp. ..
  19. Maroun C, Holgado Madruga M, Royal I, Naujokas M, Fournier T, Wong A, et al. The Gab1 PH domain is required for localization of Gab1 at sites of cell-cell contact and epithelial morphogenesis downstream from the met receptor tyrosine kinase. Mol Cell Biol. 1999;19:1784-99 pubmed
    ..We have previously shown that Gab1 is the major phosphorylated protein following stimulation of the Met receptor in epithelial cells that undergo a ..
  20. Lock L, Royal I, Naujokas M, Park M. Identification of an atypical Grb2 carboxyl-terminal SH3 domain binding site in Gab docking proteins reveals Grb2-dependent and -independent recruitment of Gab1 to receptor tyrosine kinases. J Biol Chem. 2000;275:31536-45 pubmed
    ..b>Gab1 acts downstream from the Met-hepatocyte growth factor receptor, and Gab1 overexpression promotes Met-dependent ..
  21. Caron C, Spring K, Laramée M, Chabot C, Cloutier M, Gu H, et al. Non-redundant roles of the Gab1 and Gab2 scaffolding adapters in VEGF-mediated signalling, migration, and survival of endothelial cells. Cell Signal. 2009;21:943-53 pubmed publisher
    b>Gab1 was previously described as a positive modulator of Akt, Src, ERK1/2, endothelial cell migration, and capillary formation in response to vascular endothelial growth factor (VEGF)...
  22. Yart A, Laffargue M, Mayeux P, Chretien S, Peres C, Tonks N, et al. A critical role for phosphoinositide 3-kinase upstream of Gab1 and SHP2 in the activation of ras and mitogen-activated protein kinases by epidermal growth factor. J Biol Chem. 2001;276:8856-64 pubmed
    ..In addition, we have observed that the docking protein Gab1, which is involved in PI3K activation during EGF stimulation, is also implicated in this pathway downstream of PI3K...
  23. Kumarswamy R, Volkmann I, Beermann J, Napp L, Jabs O, Bhayadia R, et al. Vascular importance of the miR-212/132 cluster. Eur Heart J. 2014;35:3224-31 pubmed publisher
    ..miRNA-cross-talk involving miR-30a-3p and miR-212, which led to suppression of important endothelial genes such as GAB1 and SIRT1 finally culminating in impaired endothelial function; and (ii) microRNAs may have different biological ..
  24. Du Z, Caenepeel S, Shen Y, Rex K, Zhang Y, He Y, et al. Preclinical Evaluation of AMG 337, a Highly Selective Small Molecule MET Inhibitor, in Hepatocellular Carcinoma. Mol Cancer Ther. 2016;15:1227-37 pubmed publisher
    ..However, the dose-dependent inhibition of downstream effectors of HGF/MET signaling, including p-GAB1, p-AKT, and p-ERK, was limited to those cell lines sensitive to AMG 337 in a viability assay (MHCC97H and HCCLM3)...
  25. Kurokawa K, Iwashita T, Murakami H, Hayashi H, Kawai K, Takahashi M. Identification of SNT/FRS2 docking site on RET receptor tyrosine kinase and its role for signal transduction. Oncogene. 2001;20:1929-38 pubmed
    ..Whereas SHC bound to RET was associated with GRB2 and GAB1 proteins, SNT/FRS2 was associated with GRB2 only, suggesting that SNT/FRS2 is involved mainly in the activation of ..
  26. Rajadurai C, Havrylov S, Zaoui K, Vaillancourt R, Stuible M, Naujokas M, et al. Met receptor tyrosine kinase signals through a cortactin-Gab1 scaffold complex, to mediate invadopodia. J Cell Sci. 2012;125:2940-53 pubmed publisher
    ..Using both GRB2-associated-binding protein 1 (Gab1)-null fibroblasts and specific knockdown of Gab1 in tumor cells we show that Met-mediated invadopodia formation and ..
  27. Jiang B, Deng Q, Huo Y, Li W, Shibuya M, Luo J. Endothelial Gab1 deficiency aggravates splenomegaly in portal hypertension independent of angiogenesis. Am J Physiol Gastrointest Liver Physiol. 2015;308:G416-26 pubmed publisher
    ..In this study, we demonstrated that endothelial Grb-2-associated binder 1 (Gab1) plays a negative role in PH-associated splenomegaly independent of angiogenesis...
  28. Lara M, Holland W, Chinn D, Burich R, Lara P, Gandara D, et al. Preclinical Evaluation of MET Inhibitor INC-280 With or Without the Epidermal Growth Factor Receptor Inhibitor Erlotinib in Non-Small-Cell Lung Cancer. Clin Lung Cancer. 2017;18:281-285 pubmed publisher
    ..Immunoblotting was used to monitor expression of EGFR/pEGFR, MET/pMET, GAB1/pGAB1, AKT/pAKT, and ERK/pERK as well as markers of apoptosis (PARP and capase-3 cleavage) in H1666, HCC827, and ..
  29. Arner P, Sahlqvist A, Sinha I, Xu H, Yao X, Waterworth D, et al. The epigenetic signature of systemic insulin resistance in obese women. Diabetologia. 2016;59:2393-2405 pubmed publisher
    ..in pathways related to integrin cell surface interactions and insulin signalling and included COL5A1, GAB1, IRS2, PFKFB3 and PTPRJ...
  30. Bouscary D, Lecoq Lafon C, Chretien S, Zompi S, Fichelson S, Muller O, et al. Role of Gab proteins in phosphatidylinositol 3-kinase activation by thrombopoietin (Tpo). Oncogene. 2001;20:2197-204 pubmed
    In this study, we show that upon thrombopoietin (Tpo) stimulation the two adapter proteins Gab1 and Gab2 are strongly tyrosine phosphorylated and associated with Shc, SHP2, PI 3-kinase and Grb2 in mpl-expressing UT7 cells...
  31. Wolf A, Eulenfeld R, Bongartz H, Hessenkemper W, Simister P, Lievens S, et al. MAPK-induced Gab1 translocation to the plasma membrane depends on a regulated intramolecular switch. Cell Signal. 2015;27:340-52 pubmed publisher
    ..Deregulated Gab1 activation and membrane binding have been observed in some haematopoietic malignancies and solid tumours, thereby ..
  32. Braun L, Ghebrehiwet B, Cossart P. gC1q-R/p32, a C1q-binding protein, is a receptor for the InlB invasion protein of Listeria monocytogenes. EMBO J. 2000;19:1458-66 pubmed
    ..entry of the bacterium into mammalian cells by stimulating tyrosine phosphorylation of the adaptor proteins Gab1, Cbl and Shc, and activation of phosphatidyl- inositol (PI) 3-kinase...
  33. McDonald C, El Hokayem J, Zafar N, Balke J, Bhat V, Mikles D, et al. Allostery mediates ligand binding to Grb2 adaptor in a mutually exclusive manner. J Mol Recognit. 2013;26:92-103 pubmed publisher
    ..Herein, using various biophysical tools, we demonstrate that although Sos1 nucleotide exchange factor and Gab1 docking protein recognize two non-overlapping sites within the Grb2 adaptor, allostery promotes the formation of ..
  34. Batth T, Papetti M, Pfeiffer A, Tollenaere M, Francavilla C, Olsen J. Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling. Cell Rep. 2018;22:2784-2796 pubmed publisher
    ..hundreds of Shp-2-dependent targets and putative substrates, including Rasa1 and Cortactin with increased pTyr and Gab1 and Erk1/2 with decreased pTyr...
  35. Hu L, Liu R. Expression of Gab1 Is Associated with Poor Prognosis of Patients with Epithelial Ovarian Cancer. Tohoku J Exp Med. 2016;239:177-84 pubmed publisher
    ..Grb2-associated binding protein 1 (Gab1) is involved in cell proliferation, and its expression may enhance the carcinogenesis and cancer progression...
  36. Fan G, Zhang S, Gao Y, Greer P, Tonks N. HGF-independent regulation of MET and GAB1 by nonreceptor tyrosine kinase FER potentiates metastasis in ovarian cancer. Genes Dev. 2016;30:1542-57 pubmed publisher
    ..of RAC1/PAK1 and promoted a kinase-independent scaffolding function that led to recruitment and phosphorylation of GAB1 and the specific activation of the SHP2-ERK signaling pathway...
  37. Jung J, Kim H, Sohn K, Kim M, Lee K. Translationally controlled tumor protein induces human breast epithelial cell transformation through the activation of Src. Oncogene. 2011;30:2264-74 pubmed publisher
    ..These findings suggest that TCTP induces tumorigenesis through distinct multicellular signaling pathways involving Src-dependent EGFR transactivation, ROS generation and MMP expression. ..
  38. Liu H, Li G, Zeng W, Zhang P, Fan F, Tu Y, et al. Combined detection of Gab1 and Gab2 expression predicts clinical outcome of patients with glioma. Med Oncol. 2014;31:77 pubmed publisher
    Grb2-associated binder 1 (Gab1) and Gab2 play important roles in cancer cell signaling...
  39. Garay C, Judge G, Lucarelli S, Bautista S, Pandey R, Singh T, et al. Epidermal growth factor-stimulated Akt phosphorylation requires clathrin or ErbB2 but not receptor endocytosis. Mol Biol Cell. 2015;26:3504-19 pubmed publisher
    ..by siRNA gene silencing, with the clathrin inhibitor pitstop2, or knocksideways silencing inhibited EGF-simulated Gab1 and Akt phosphorylation in ARPE-19 cells...
  40. Chlapek P, Zitterbart K, Kren L, Filipová L, Sterba J, Veselska R. Uniformity under in vitro conditions: Changes in the phenotype of cancer cell lines derived from different medulloblastoma subgroups. PLoS ONE. 2017;12:e0172552 pubmed publisher
    ..these groups are thought to be distinguishable using the immunohistochemical detection of ?-catenin, filamin A, GAB1 and YAP1 protein markers...
  41. Juszczak G, Stankiewicz A. Glucocorticoids, genes and brain function. Prog Neuropsychopharmacol Biol Psychiatry. 2018;82:136-168 pubmed publisher
    ..up-regulation was associated with the altered transcription of genes regulating growth factor and mTORC1 signaling (Gab1, Tsc22d3, Dusp1, Ndrg2, Ppp5c and Sesn1) and progression of the cell cycle (Ccnd1, Cdkn1a and Cables1)...
  42. Zhang Y, Xu Y, Liu S, Guo X, Cen D, Xu J, et al. Scaffolding protein Gab1 regulates myeloid dendritic cell migration in allergic asthma. Cell Res. 2016;26:1226-1241 pubmed publisher
    ..Recent studies identified genetic variants of human GAB1 as a novel asthma susceptibility factor. However, the functions of Gab1 in lung remain largely unexplored...
  43. Deng H, Fung G, Qiu Y, Wang C, Zhang J, Jin Z, et al. Cleavage of Grb2-Associated Binding Protein 2 by Viral Proteinase 2A during Coxsackievirus Infection. Front Cell Infect Microbiol. 2017;7:85 pubmed publisher
    ..We have previously demonstrated that Grb2-associated binding protein 1 (GAB1), a signaling adaptor protein that serves as a platform for intracellular signaling assembly and transduction, is ..
  44. Kanai M, Göke M, Tsunekawa S, Podolsky D. Signal transduction pathway of human fibroblast growth factor receptor 3. Identification of a novel 66-kDa phosphoprotein. J Biol Chem. 1997;272:6621-8 pubmed
    ..pp66.GRB2.Sos; these two complexes may alternatively link FGFG3 to mitogen-activated protein kinase. Finally, activated FGFR3 was also found to result in phosphorylation of phospholipase C-gamma but reduced phosphorylation of c-Src. ..
  45. Onishi Haraikawa Y, Funaki M, Gotoh N, Shibuya M, Inukai K, Katagiri H, et al. Unique phosphorylation mechanism of Gab1 using PI 3-kinase as an adaptor protein. Biochem Biophys Res Commun. 2001;288:476-82 pubmed
    Grb2-associated binder-1 (Gab1) undergoes tyrosine phosphorylation in response to stimulation by growth factors and hormones including insulin, epidermal growth factor (EGF), nerve growth factor (NGF), and hepatocyte growth factor (HGF)...
  46. Wang J, Song W, Shen W, Yang X, Sun W, Qu S, et al. MicroRNA-200a Suppresses Cell Invasion and Migration by Directly Targeting GAB1 in Hepatocellular Carcinoma. Oncol Res. 2017;25:1-10 pubmed publisher
    ..Furthermore, bioinformatics and luciferase reporter assays indicated that GAB1 is a direct target of miR-200a...
  47. Koncz G, Bodor C, Kovesdi D, Gáti R, Sarmay G. BCR mediated signal transduction in immature and mature B cells. Immunol Lett. 2002;82:41-9 pubmed
    ..we have found a significant difference in the tyrosine phosphorylation of the Gab family adaptor proteins, Gab1/2...
  48. Fukumoto T, Kubota Y, Kitanaka A, Yamaoka G, Ohara Waki F, Imataki O, et al. Gab1 transduces PI3K-mediated erythropoietin signals to the Erk pathway and regulates erythropoietin-dependent proliferation and survival of erythroid cells. Cell Signal. 2009;21:1775-83 pubmed publisher
    In this study, we examined the biological functions of Gab1 in erythropoietin receptor (EPOR)-mediated signaling in vivo...
  49. Lewitzky M, Kardinal C, Gehring N, Schmidt E, Konkol B, Eulitz M, et al. The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif. Oncogene. 2001;20:1052-62 pubmed
    ..b>Gab1, a receptor tyrosine kinase substrate which associates with Grb2 and the c-Met receptor, was previously shown to ..
  50. Shi T, Niepel M, McDermott J, Gao Y, Nicora C, Chrisler W, et al. Conservation of protein abundance patterns reveals the regulatory architecture of the EGFR-MAPK pathway. Sci Signal. 2016;9:rs6 pubmed publisher
    ..abundance of most core proteins was between 50,000 and 70,000 copies per cell, but the adaptors SOS1, SOS2, and GAB1 were found at far lower amounts (2000 to 5000 copies per cell)...
  51. Kang H, Chung D, Sung C, Yoo S, Yu E, Kim N, et al. SHP2 is induced by the HBx-NF-κB pathway and contributes to fibrosis during human early hepatocellular carcinoma development. Oncotarget. 2017;8:27263-27276 pubmed publisher
    ..EGF treatment induced ERK activation as well as the rapid assembly of SHP2, EGFR, and Gab1. Upon LPS stimulation, NF-κB-SHP2-ERK activation and phosphorylated STAT3 levels exhibited a negative ..
  52. Ren Y, Meng S, Mei L, Zhao Z, Jove R, Wu J. Roles of Gab1 and SHP2 in paxillin tyrosine dephosphorylation and Src activation in response to epidermal growth factor. J Biol Chem. 2004;279:8497-505 pubmed
    ..We found that Gab1, a docking protein for the SHP2 protein-tyrosine phosphatase in EGF-stimulated cells, was associated with paxillin...
  53. Zhou L, Talebian A, Meakin S. The signaling adapter, FRS2, facilitates neuronal branching in primary cortical neurons via both Grb2- and Shp2-dependent mechanisms. J Mol Neurosci. 2015;55:663-77 pubmed publisher
    ..With FRS2 mutants deficient in Grb2 or Shp2 binding, we demonstrate that FRS2 binds Gab1 and Gab2 through Grb2, providing an alternative route to activate PI3 kinase and Shp2...
  54. Sang H, Li T, Li H, Liu J. Gab1 regulates proliferation and migration through the PI3K/Akt signaling pathway in intrahepatic cholangiocarcinoma. Tumour Biol. 2015;36:8367-77 pubmed publisher
    ..Prognosis is poor due to lack of effective comprehensive treatments. In this study, we assessed the expression of Gab1, VEGFR-2, and MMP-9 in intrahepatic cholangiocarcinoma solid tumors by immunohistochemistry and determined whether ..
  55. Ong S, Dilworth S, Hauck Schmalenberger I, Pawson T, Kiefer F. ShcA and Grb2 mediate polyoma middle T antigen-induced endothelial transformation and Gab1 tyrosine phosphorylation. EMBO J. 2001;20:6327-36 pubmed
    ..PymT mimics activated receptor tyrosine kinases by forming a ShcA-Grb2-Gab1 complex, thus inducing Gab1 tyrosine phosphorylation, which itself is associated with PI3K...
  56. Meng L. Essential role of polymorphism of Gab1, EGFR, and EGF for the susceptibility of biliary tract cancer. Tumour Biol. 2014;35:12497-508 pubmed publisher
    ..of BTC by analyzing frequency distribution of genotypes and alleles of GRB2-associated-binding protein 1 (Gab1), endothelial growth factor receptor (EGFR), and endothelial growth factor (EGF) and identified potential risk of ..
  57. van den Akker E, van Dijk T, Parren van Amelsvoort M, Grossmann K, Schaeper U, Toney Earley K, et al. Tyrosine kinase receptor RON functions downstream of the erythropoietin receptor to induce expansion of erythroid progenitors. Blood. 2004;103:4457-65 pubmed
    ..We studied the roles of the docking molecules Grb2-associated binder-1 (Gab1) and Gab2 in EPO-induced signal transduction and erythropoiesis...
  58. Berry D, Nash P, Liu S, Pawson T, McGlade C. A high-affinity Arg-X-X-Lys SH3 binding motif confers specificity for the interaction between Gads and SLP-76 in T cell signaling. Curr Biol. 2002;12:1336-41 pubmed
    ..These results provide a molecular explanation for the specific role of Gads in T cell receptor signaling, and identify a discrete subclass of SH3 domains whose binding is dependent on a core R-X-X-K motif. ..
  59. Kallin A, Demoulin J, Nishida K, Hirano T, Ronnstrand L, Heldin C. Gab1 contributes to cytoskeletal reorganization and chemotaxis in response to platelet-derived growth factor. J Biol Chem. 2004;279:17897-904 pubmed
    b>Gab1 is a scaffolding/docking protein that has been suggested to play a role in signal transduction downstream of certain plasma membrane receptors, including platelet-derived growth factor (PDGF) receptors...
  60. Adachi Y, Watanabe K, Kita K, Kitai H, Kotani H, Sato Y, et al. Resistance mediated by alternative receptor tyrosine kinases in FGFR1-amplified lung cancer. Carcinogenesis. 2017;38:1063-1072 pubmed publisher
    ..activation of AKT and extracellular signal-regulated kinase by MET signaling that was mediated by GRB2 associated binding protein 1 (GAB1)...
  61. Podar K, Mostoslavsky G, Sattler M, Tai Y, Hayashi T, Catley L, et al. Critical role for hematopoietic cell kinase (Hck)-mediated phosphorylation of Gab1 and Gab2 docking proteins in interleukin 6-induced proliferation and survival of multiple myeloma cells. J Biol Chem. 2004;279:21658-65 pubmed
    ..In this report we show that Grb2-associated binder (Gab) family adapter proteins Gab1 and Gab2 are expressed by multiple myeloma cells; and that interleukin-6 induces their tyrosine phosphorylation and ..
  62. Tan W, Popel A, Mac Gabhann F. Computational Model of Gab1/2-Dependent VEGFR2 Pathway to Akt Activation. PLoS ONE. 2013;8:e67438 pubmed publisher
    ..and validated the first computational model of VEGFR2 trafficking and signaling, to study the opposing roles of Gab1 and Gab2 in regulation of Akt phosphorylation in VEGF-stimulated endothelial cells...
  63. Lucarelli S, Delos Santos R, Antonescu C. Measurement of Epidermal Growth Factor Receptor-Derived Signals Within Plasma Membrane Clathrin Structures. Methods Mol Biol. 2017;1652:191-225 pubmed publisher
    ..such as the activation of phosphatidylinositol-3-kinase (PI3K) and Akt, a process requiring the phosphorylation of Gab1. While the identity of many signals that can be activated by EGFR has been revealed, how the spatiotemporal ..
  64. Lehr S, Kotzka J, Avci H, Sickmann A, Meyer H, Herkner A, et al. Identification of major ERK-related phosphorylation sites in Gab1. Biochemistry. 2004;43:12133-40 pubmed
    b>Gab1 (Grb2-associated binder1) belongs to a family of multifunctional docking proteins that play a central role in the integration of receptor tyrosine kinase (RTK) signaling, i.e...
  65. Oneyama C, Nakano H, Sharma S. UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction blocking drug. Oncogene. 2002;21:2037-50 pubmed
    ..such as Grb2-Sos1, cortactin-ZO1, as well as atypical SH3-mediated protein-protein interactions such as Grb2-Gab1. However, UCS15A was unable to disrupt the non-SH3-mediated protein-protein interactions of beta-catenin, with E-..
  66. Nakaoka Y, Nishida K, Fujio Y, Izumi M, Terai K, Oshima Y, et al. Activation of gp130 transduces hypertrophic signal through interaction of scaffolding/docking protein Gab1 with tyrosine phosphatase SHP2 in cardiomyocytes. Circ Res. 2003;93:221-9 pubmed
    Grb2-associated binder-1 (Gab1) is a scaffolding/docking protein and contains a Pleckstrin homology domain and potential binding sites for Src homology (SH) 2 and SH3 domains...
  67. Wickrema A, Uddin S, Sharma A, Chen F, Alsayed Y, Ahmad S, et al. Engagement of Gab1 and Gab2 in erythropoietin signaling. J Biol Chem. 1999;274:24469-74 pubmed
    ..In the present study we provide evidence that the recently cloned IRS-related proteins, Gab1 and Gab2, of the Gab family of proteins, are rapidly phosphorylated on tyrosine during erythropoietin treatment of ..
  68. Roemer K, Young S, Savaris R. Characterization of GAB1 expression over the menstrual cycle in women with and without polycystic ovarian syndrome provides a new insight into its pathophysiology. J Clin Endocrinol Metab. 2014;99:E2162-8 pubmed publisher
    In a previous microarray analysis, GRB2-associated binding protein 1 (GAB1), a docking protein closely related to the insulin receptor substrate, was down-regulated in endometrium of women with polycystic ovary syndrome (PCOS)...
  69. Gill K, Macdonald Obermann J, Pike L. Epidermal growth factor receptors containing a single tyrosine in their C-terminal tail bind different effector molecules and are signaling-competent. J Biol Chem. 2017;292:20744-20755 pubmed publisher
    ..The ability of the single-Tyr receptors to signal correlated with their ability to bind Gab1 (Grb2-associated binding protein 1)...
  70. Furcht C, Buonato J, Lazzara M. EGFR-activated Src family kinases maintain GAB1-SHP2 complexes distal from EGFR. Sci Signal. 2015;8:ra46 pubmed publisher
    ..in the interactions among the epidermal growth factor (EGF) receptor (EGFR), GRB2-associated binder protein 1 (GAB1), and SH2 domain-containing phosphatase 2 (SHP2) affected EGFR signaling output, specifically SHP2 binding to ..
  71. Chang C, Chan P, Li J, Chen C, Shieh J, Fu Y, et al. Gab1 is essential for membrane translocation, activity and integrity of mTORCs after EGF stimulation in urothelial cell carcinoma. Oncotarget. 2015;6:1478-89 pubmed
    ..Here, we demonstrate that Gab1 is an important upstream regulator in EGF-mediated activation of mTORCs...
  72. Chen L, Du Cuny L, Moses S, Dumas S, Song Z, Rezaeian A, et al. Novel inhibitors induce large conformational changes of GAB1 pleckstrin homology domain and kill breast cancer cells. PLoS Comput Biol. 2015;11:e1004021 pubmed publisher
    The Grb2-associated binding protein 1 (GAB1) integrates signals from different signaling pathways and is over-expressed in many cancers, therefore representing a new therapeutic target...
  73. Cherif M, Caputo M, Nakaoka Y, Angelini G, Ghorbel M. Gab1 Is Modulated by Chronic Hypoxia in Children with Cyanotic Congenital Heart Defect and Its Overexpression Reduces Apoptosis in Rat Neonatal Cardiomyocytes. Biomed Res Int. 2015;2015:718492 pubmed publisher
    Gab1 (Grb2 associated binding protein 1) is a member of the scaffolding/docking proteins (Gab1, Gab2, and Gab3). It is required for fibroblast cell survival and maintaining cardiac function...
  74. Montagner A, Yart A, Dance M, Perret B, Salles J, Raynal P. A novel role for Gab1 and SHP2 in epidermal growth factor-induced Ras activation. J Biol Chem. 2005;280:5350-60 pubmed
    SHP2 was recently found to down-regulate PI3K activation by dephosphorylating Gab1 but the mechanisms explaining the positive role of the Gab1/SHP2 pathway in EGF-induced Ras activation remain ill defined...
  75. Mouradian M, Kikawa K, Johnson E, Beck K, Pardini R. Key roles for GRB2-associated-binding protein 1, phosphatidylinositol-3-kinase, cyclooxygenase 2, prostaglandin E2 and transforming growth factor alpha in linoleic acid-induced upregulation of lung and breast cancer cell growth. Prostaglandins Leukot Essent Fatty Acids. 2014;90:105-115 pubmed publisher
    ..cell lines greatly increased the association between the scaffolding protein GRB2-associated-binding protein 1 (Gab1) and epidermal growth factor receptor (EGFR), although Gab1 protein levels were significantly decreased...
  76. Rathnakumar K, Savant S, Giri H, Ghosh A, Fisslthaler B, Fleming I, et al. Angiopoietin-2 mediates thrombin-induced monocyte adhesion and endothelial permeability. J Thromb Haemost. 2016;14:1655-67 pubmed publisher
    ..Down-regulation of the adaptor protein Gab1, a co-activator of SHP2, as well as overexpression of the Gab1 mutant incapable of interacting with SHP2 (YFGab1), ..
  77. Petrelli A, Gilestro G, Lanzardo S, Comoglio P, Migone N, Giordano S. The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met. Nature. 2002;416:187-90 pubmed
    ..These data provide further evidence of a relationship between receptor-mediated signalling and endocytosis, and disclose a novel functional role for Cbl in HGF receptor signalling. ..
  78. Hirota T, Takahashi A, Kubo M, Tsunoda T, Tomita K, Doi S, et al. Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population. Nat Genet. 2011;43:893-6 pubmed publisher
    ..histocompatibility complex and TSLP-WDR36 loci previously reported, we identified three additional loci: a USP38-GAB1 locus on chromosome 4q31 (combined P = 1.87 × 10(-12)), a locus on chromosome 10p14 (P = 1...
  79. Maeda K, Murakami H, Yoshida R, Ichihara M, Abe A, Hirai M, et al. Biochemical and biological responses induced by coupling of Gab1 to phosphatidylinositol 3-kinase in RET-expressing cells. Biochem Biophys Res Commun. 2004;323:345-54 pubmed
    Grb2-associated binder-1 (Gab1) is a docking protein closely related to insulin receptor substrates...
  80. Mraz M, Chen L, Rassenti L, Ghia E, Li H, Jepsen K, et al. miR-150 influences B-cell receptor signaling in chronic lymphocytic leukemia by regulating expression of GAB1 and FOXP1. Blood. 2014;124:84-95 pubmed publisher
    ..miR-150 expressed relatively higher levels of forkhead box P1 (FOXP1) and GRB2-associated binding protein 1 (GAB1), genes with 3' untranslated regions having evolutionary-conserved binding sites for miR-150...
  81. Bertagnolo V, Marchisio M, Volinia S, Caramelli E, Capitani S. Nuclear association of tyrosine-phosphorylated Vav to phospholipase C-gamma1 and phosphoinositide 3-kinase during granulocytic differentiation of HL-60 cells. FEBS Lett. 1998;441:480-4 pubmed
    ..The role of the Vav/phospholipase C-gamma1/phosphoinositide 3-kinase phosphoprotein complexes in the nuclei of HL-60 induced to differentiate along the granulocytic lineage is discussed. ..
  82. Kameda H, Risinger J, Han B, Baek S, Barrett J, Glasgow W, et al. Identification of epidermal growth factor receptor- Grb2-associated binder-1-SHP-2 complex formation and its functional loss during neoplastic cell progression. Cell Growth Differ. 2001;12:307-18 pubmed
    The adaptor protein Grb2-associated binder-1 (Gab1) is known to bind to the SHP-2 tyrosine phosphatase on epidermal growth factor (EGF) receptor stimulation...
  83. Feng J, Xue S, Pang Q, Rang Z, Cui F. miR-141-3p inhibits fibroblast proliferation and migration by targeting GAB1 in keloids. Biochem Biophys Res Commun. 2017;490:302-308 pubmed publisher
    ..Growth factor receptor binding 2-associated binding protein 1 (GAB1) was identified and confirmed as a direct target of miR-141-3p...
  84. Landry M, Pomerleau V, Saucier C. Non-canonical dynamic mechanisms of interaction between the p66Shc protein and Met receptor. Biochem J. 2016;473:1617-27 pubmed publisher
    ..p66Shc interacts constitutively with the receptor Met, and the Grb2 (growth factor receptor-bound protein-2) and Gab1 (Grb2-associated binder-1) adaptor proteins...
  85. Deng H, Fung G, Shi J, Xu S, Wang C, Yin M, et al. Enhanced enteroviral infectivity via viral protease-mediated cleavage of Grb2-associated binder 1. FASEB J. 2015;29:4523-31 pubmed publisher
    ..However, the detail mechanism remains largely unknown. Grb2-associated binder 1 (GAB1) is an important docking protein responsible for intracellular signaling assembly and transduction...