Affinage

GAB1

GRB2-associated-binding protein 1 · UniProt Q13480

Length
694 aa
Mass
76.6 kDa
Annotated
2026-04-28
100 papers in source corpus 46 papers cited in narrative 44 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GAB1 is a multi-site docking protein that integrates and amplifies signaling downstream of receptor tyrosine kinases (Met, EGFR, insulin receptor, PDGFR, KGFR), cytokine receptors (gp130, BCR), and non-receptor kinases (FER, Src family kinases) to control morphogenesis, migration, proliferation, polarity, and vascular function. Recruited to activated receptors via Grb2 SH3-domain binding and a unique 13-amino-acid Met-binding domain, GAB1 is tyrosine-phosphorylated on defined residues that create docking sites for SHP2 (pY627/pY659 bisphosphoryl activation motif), PI3K p85 (Y447/Y472/Y619 YXXM motifs), PLCγ, Crk, PAK4, and cortactin, thereby activating Ras/ERK, PI3K/Akt, JNK, eNOS/PKA, and Wnt/β-catenin effector pathways (PMID:8906793, PMID:11323411, PMID:10978177, PMID:10618718, PMID:16284184, PMID:31944179). Its PH domain binds PIP3 to enforce a positive-feedback membrane recruitment loop that is counterbalanced by ERK-mediated serine/threonine phosphorylation (S454/S581/S597) reducing PI3K binding and by SHP2-catalyzed dephosphorylation of the RasGAP-docking site Y317 to sustain Ras activation (PMID:10022866, PMID:15379552, PMID:15574420, PMID:19050043). A recessive GAB1 PH-domain missense variant (p.Gly116Glu) causes DFNB26 profound deafness, modifiable by the METTL13 suppressor allele (PMID:29408807).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1996 High

    Identification of GAB1 as a direct Met receptor substrate with a unique Met-binding domain resolved how a single scaffold could mediate Met-specific branching morphogenesis independently of other adaptor proteins.

    Evidence Co-immunoprecipitation and mutational analysis in MDCK epithelial morphogenesis assay

    PMID:8906793

    Open questions at the time
    • The structure of the Met-binding domain was not resolved
    • Whether GAB1 interacted with other RTKs was unknown
  2. 1997 High

    Demonstrating that Met–GAB1 coupling requires Grb2 binding at Met Y1356 and that GAB1 is the major Met kinase substrate established the dual (direct + Grb2-bridged) recruitment mechanism and the functional indispensability of GAB1 for tubulogenesis.

    Evidence In vitro kinase assays, co-immunoprecipitation with Met point mutants, tubulogenesis assays

    PMID:9252406 PMID:9444958

    Open questions at the time
    • Relative contributions of direct vs. Grb2-mediated recruitment in vivo were not quantified
  3. 1998 High

    Mapping insulin-receptor-phosphorylated GAB1 tyrosines to PI3K-p85 (Y472, Y447, Y589) and SHP2 (Y627) binding sites defined the general phosphotyrosine code by which GAB1 recruits distinct effectors.

    Evidence Modified yeast two-hybrid with IR kinase, site-directed mutagenesis, cellular co-immunoprecipitation

    PMID:9658397

    Open questions at the time
    • Whether these assignments held for other RTKs was only partially tested
  4. 1999 High

    Multiple studies resolved key effector pathways: (i) PH domain binding to PIP3 drives membrane localization in a PI3K-dependent positive feedback loop; (ii) EGFR phosphorylates eight GAB1 tyrosines with Y657 as the major SHP2-binding site; (iii) Crk recruitment to phospho-GAB1 activates JNK/AP-1/MMP-1; (iv) activated ERK2 directly binds and serine-phosphorylates GAB1, establishing ERK as both an effector and a feedback regulator.

    Evidence Phospholipid binding assays, PH-domain mutagenesis, in vitro EGFR kinase with mass spectrometry, co-IP with dominant-negative Crk, pulldown with purified pERK2

    PMID:10022866 PMID:10593929 PMID:10618718 PMID:9890893

    Open questions at the time
    • Whether ERK-mediated serine phosphorylation was activating or inhibitory was context-dependent and not fully resolved
  5. 2000 High

    Gab1 knockout mice phenocopied Met/HGF nulls (absent diaphragm, impaired muscle progenitor migration, reduced liver, placental defect), providing definitive in vivo genetic proof that GAB1 is essential for Met signaling during development; concurrently, PLCγ recruitment to GAB1 Y307/Y373/Y407 was shown to be required for sustained HGF-induced tubulogenesis.

    Evidence Targeted gene knockout in mouse, histological analysis, 32P-peptide mapping and triple Y→F mutagenesis in MDCK cells

    PMID:10734310 PMID:10913131 PMID:10995442

    Open questions at the time
    • Tissue-specific contributions of individual effector arms were not dissected in vivo
  6. 2001 High

    The bisphosphoryl tyrosine-based activation motif (BTAM; pY627/pY659) was shown to activate SHP2 phosphatase and a GAB1–SHP2 chimera sufficed for ERK activation, establishing that physical recruitment and activation of SHP2 by GAB1 is necessary and sufficient for the Ras/ERK cascade; simultaneously, GAB1 was found to link BCR to PI3K/SHP2 in B cells.

    Evidence In vitro phosphatase assays with bisphosphopeptides, chimeric protein reconstitution, far-Western with SH2 domains; PH-domain mutagenesis and confocal imaging in WEHI-231 B cells

    PMID:11278704 PMID:11323411

    Open questions at the time
    • How SHP2 substrate specificity is directed by GAB1 scaffolding in vivo was unclear
  7. 2002 High

    Context-dependent feedback was revealed: EGF-stimulated ERK promotes SHP2-dependent dephosphorylation of GAB1 to reduce PI3K/Akt, opposite to the positive ERK→PI3K effect seen with HGF, showing that the same scaffold produces divergent outputs depending on the activating receptor.

    Evidence MEK inhibitor, dominant-negative SHP2, co-immunoprecipitation of Gab1/p85 with PI3K/Akt readouts

    PMID:11445578 PMID:11896055

    Open questions at the time
    • Molecular basis for EGF vs. HGF context specificity in ERK-GAB1 crosstalk was not defined
  8. 2003 High

    Mechanistic dissection showed GAB1-recruited SHP2 dephosphorylates paxillin to activate Src and drives EGF-induced migration, while in oxidative stress GAB1 integrates pro-apoptotic (SHP2→JNK) and pro-survival (PI3K→Akt) arms, broadening GAB1's role beyond RTK signaling.

    Evidence Gab1FF mutants, dominant-negative SHP2, Gab1−/− MEFs with adenoviral reconstitution, Src kinase and cell migration assays, H2O2-induced JNK/ERK/p38 assays

    PMID:12808090 PMID:14665621

    Open questions at the time
    • Identity of additional SHP2 substrates recruited via GAB1 was incomplete
  9. 2004 High

    Two breakthroughs completed the negative-feedback picture: SHP2 dephosphorylates GAB1 Y317 to disengage RasGAP and sustain Ras activation; ERK phosphorylates six GAB1 Ser/Thr sites flanking YXXM motifs to reduce PI3K binding.

    Evidence Substrate-trapping SHP2 mutant, Y317F GAB1 mutant, Ras-GTP assays; in vitro ERK1/2 kinase assay with mass spectrometry phosphosite mapping

    PMID:15379552 PMID:15574420

    Open questions at the time
    • Temporal dynamics and stoichiometry of these competing phosphorylation events in living cells were not measured
  10. 2005 High

    In vivo tissue-specific knockouts demonstrated that hepatic GAB1 negatively modulates insulin signaling via ERK-dependent IRS-1 serine phosphorylation, and GAB1/CXCR4 genetic interaction controls tongue muscle progenitor migration, extending GAB1's roles to metabolism and chemokine signaling.

    Evidence Liver-specific conditional KO with glucose tolerance tests; double-mutant CXCR4;Gab1 mouse analysis

    PMID:15821749 PMID:16166380 PMID:16284184

    Open questions at the time
    • Whether GAB1 directly modulates CXCR4 signaling biochemically or acts in parallel was not resolved
  11. 2007 High

    Knock-in mice carrying point mutations in PI3K- or SHP2-binding sites parsed effector-specific developmental roles: GAB1–PI3K is essential for EGFR-driven eyelid closure, while GAB1–SHP2 is essential for Met-driven placental and limb muscle development.

    Evidence Multiple knock-in alleles with organ-specific phenotypic scoring

    PMID:17881575

    Open questions at the time
    • Whether compensatory signaling by GAB2 modifies any knock-in phenotypes was not tested
  12. 2008 High

    ERK-dependent phosphorylation of GAB1 Ser551 was found to be required for PH-domain-mediated membrane recruitment, adding a positive regulatory layer to the PIP3-binding mechanism.

    Evidence Ser551Ala GAB1 mutant, MEK inhibitor, confocal imaging of membrane translocation

    PMID:19050043

    Open questions at the time
    • Whether Ser551 phosphorylation changes PH domain lipid affinity directly or acts via conformational change was not determined
  13. 2009 High

    PAK4 was identified as a novel GAB1 effector recruited via proline-rich motifs P4/5 at lamellipodia to promote HGF-driven cell dispersal and invasion, expanding the repertoire of GAB1-nucleated signaling complexes.

    Evidence Reciprocal co-IP, P4/5 mutagenesis, PAK4 siRNA, cell dispersal and invasion assays

    PMID:19289496

    Open questions at the time
    • PAK4 substrates downstream of GAB1 recruitment were not identified
  14. 2012 High

    Three parallel advances: (i) cortactin interacts with GAB1 P4/5 to drive invadopodia formation; (ii) GAB1 bridges PAR1–PAR3 polarity complexes and competes with PAR6 for PAR3, controlling tight junction timing and epithelial polarity; (iii) a cancer-associated T387N mutation ablates a negative-feedback phosphosite, enhancing ERK and aberrant morphogenesis.

    Evidence SH3-domain pulldowns, Gab1-null reconstitution, invadopodia imaging; PAR1 kinase assays, cyst polarity assays; mass spectrometry phosphosite mapping with 3D culture

    PMID:22366451 PMID:22751113 PMID:22883624

    Open questions at the time
    • How GAB1-polarity and GAB1-RTK signaling are coordinated temporally during morphogenesis is unknown
    • Clinical significance of T387N in cancer prognosis was not established
  15. 2015 High

    Src family kinases were shown to maintain GAB1 phosphorylation at cytosolic sites distal from EGFR, sustaining SHP2/ERK signaling beyond receptor inactivation; concurrently, cardiac-specific Gab1 KO revealed GAB1 protects against dilated cardiomyopathy under pressure overload via MAPK signaling.

    Evidence SFK inhibitors with kinetic co-IP and computational modeling; cardiac-specific conditional KO with TAC model and echocardiography

    PMID:25969544 PMID:26517531

    Open questions at the time
    • Mechanism by which SFK finds and phosphorylates cytosolic GAB1 away from membranes is unclear
  16. 2016 High

    The non-receptor kinase FER was identified as a Met-independent phosphorylator of GAB1 that activates SHP2/ERK to promote ovarian cancer metastasis, demonstrating that GAB1 activation does not require canonical RTK autophosphorylation.

    Evidence In vitro kinase assay, FER knockdown, phospho-specific Western blot, in vivo metastasis model

    PMID:27401557

    Open questions at the time
    • Whether other non-receptor kinases similarly activate GAB1 independently of RTKs was not explored
  17. 2018 High

    A PH-domain missense variant (p.Gly116Glu) in GAB1 was shown to cause DFNB26 recessive deafness, modified by a METTL13 suppressor allele that forms a complex with GAB1 and SPRY2, linking GAB1 scaffold function to human Mendelian disease.

    Evidence Human genetics, co-immunoprecipitation of GAB1/METTL13/SPRY2, zebrafish morphant rescue, patient lymphoblastoid cell signaling

    PMID:29408807

    Open questions at the time
    • Structural basis of how G116E disrupts PH domain function is not resolved
    • Whether METTL13 methyltransferase activity is required for suppression was not tested
  18. 2020 High

    GAB1 was found to control CNS myelination by binding GSK3β and regulating nuclear β-catenin accumulation in oligodendrocyte precursors, revealing a non-canonical effector arm beyond classical RTK→PI3K/MAPK signaling.

    Evidence Conditional KO in oligodendrocyte lineage (Olig2-Cre), co-IP of GAB1/GSK3β, β-catenin nuclear localization and myelination quantification

    PMID:31944179

    Open questions at the time
    • Which GAB1 domain mediates GSK3β binding is unknown
    • Whether GAB1 regulates Wnt signaling in other cell types was not investigated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Despite extensive biochemical and genetic characterization, several questions remain: how does the same scaffold produce opposing outputs (e.g., pro-migration vs. pro-survival) in different cell types; what is the atomic-resolution structure of full-length GAB1 or its key domain complexes; how do post-translational modifications beyond phosphorylation (ubiquitination, acetylation) regulate GAB1 turnover; and what is the full spectrum of human diseases caused by GAB1 coding variants.
  • No full-length crystal or cryo-EM structure of GAB1 exists
  • Ubiquitin-dependent regulation of GAB1 stability is largely uncharacterized
  • Genotype–phenotype spectrum for GAB1 variants in human disease is incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 7 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 2
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 9 R-HSA-1266738 Developmental Biology 4 R-HSA-168256 Immune System 2 R-HSA-1430728 Metabolism 1
Partners
CTTNGRB2METMETTL13PAK4PIK3R1PRKD3PTPN11
Complex memberships
GAB1–Grb2–Met complexGAB1–PAR1–PAR3 polarity complexGAB1–SHP2 signalosome

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 GAB1 interacts directly with the c-Met receptor tyrosine kinase via a newly identified proline-rich domain (Met-binding domain) that binds the bidentate phosphotyrosine docking site in c-Met; overexpression of GAB1 in epithelial cells is sufficient to induce c-Met-specific branching morphogenesis. Co-immunoprecipitation, mutational analysis, epithelial morphogenesis assay Nature High 8906793
1997 Association of GAB1 with the Met receptor requires a functional Grb2 binding site at Met tyrosine 1356; GAB1 is the major phosphorylation substrate of Met kinase in vitro and in vivo; Met mutants unable to associate with GAB1 fail to induce branching tubulogenesis. In vitro kinase assay, co-immunoprecipitation, Met receptor point mutants, tubulogenesis assay The Journal of biological chemistry High 9252406 9444958
1997 GAB1 coupling to the oncogenic Met (Tpr-Met) requires Grb2 binding and correlates with transforming potential; mutations abolishing Grb2 or Gab1 binding reduce transformation, identifying GAB1 as the major substrate of Tpr-Met. Point mutagenesis of Met docking site, co-immunoprecipitation, focus-formation/soft-agar transformation assays Oncogene High 9242692 9444958
1999 The GAB1 pleckstrin homology (PH) domain binds phosphatidylinositol 3,4,5-trisphosphate; mutation of conserved phospholipid-binding residues (W26, R29) reduces PIP3 binding, abolishes localization of GAB1 to cell-cell contact sites, and impairs Met-dependent branching tubulogenesis; PI3K activity is required for this membrane localization. Phospholipid binding assay, site-directed mutagenesis of PH domain, confocal microscopy, PI3K inhibitor (LY294002), morphogenesis assay Molecular and cellular biology / The Journal of biological chemistry High 10022866 10531383
2000 GAB1 associates constitutively with Grb2 via two sites: a canonical PXXP SH3-binding motif and a novel PX(V/I)(D/N)RXXKP motif in the Met-binding domain; the c-Met binding site is localized to a 13-amino-acid region unique to GAB1 sufficient to confer Met-binding on GAB2; interaction with SHP2 (not PI3K, CRKL, or Shc) is essential for branching morphogenesis. Reverse yeast two-hybrid mapping, domain swap experiments, MDCK branching morphogenesis assay The Journal of cell biology High 10871282
2000 Gab1-null mice phenocopy c-Met/HGF mutant mice: muscle precursor migration to limbs is impaired, diaphragm muscles are absent, liver size is reduced, and placental labyrinth layer is severely deficient, providing in vivo genetic evidence that GAB1 is essential for c-Met signaling. Targeted gene knockout in mouse, histological and embryological analysis, genetic interaction with c-Met heterozygosity The Journal of cell biology High 10995442
2000 GAB1 is recruited to the EGF receptor in a Grb2-dependent manner, whereas recruitment to Met is both Grb2-dependent and Grb2-independent (via the Met-binding domain PXXXR/PX3RX2KPX7PLD motif); the two mechanisms reflect distinct biological functions downstream of each receptor. Mapping of Grb2 C-terminal SH3-binding sites, co-immunoprecipitation, pulldown competition The Journal of biological chemistry High 10913131
2001 Phosphotyrosines 627 and 659 of GAB1 constitute a bisphosphoryl tyrosine-based activation motif (BTAM): the N-SH2 domain of SHP2 binds pY627 and the C-SH2 binds pY659; a bisphosphopeptide containing both sites activates SHP2 phosphatase; GAB1 is itself a substrate of SHP2; a Gab1FF-SHP2ΔN chimera constitutively activates ERK2, demonstrating that physical association of activated SHP2 with GAB1 is necessary and sufficient for ERK activation. Site-directed mutagenesis, far-Western blot with isolated SH2 domains, in vitro phosphatase assay with peptide substrates, substrate-trapping, chimeric protein reconstitution, ERK2 activation assay The Journal of biological chemistry High 11323411
2001 The Grb2 C-terminal SH3 domain binds a 13-amino-acid atypical motif (PXXXRXXKP) in GAB1 (and SLP-76) that lacks the canonical PxxP core; mapped by tryptophan fluorescence spectrometry and in vitro competition with synthetic peptides. Peptide synthesis, tryptophan fluorescence spectrometry, in vitro domain precipitation competition Oncogene High 11314042
1999 Activated (phosphorylated) ERK2 directly associates with GAB1 via the Met-binding domain independently of a third protein; ERK2 phosphorylates GAB1 in vitro on serine residues; co-expression of constitutively active MEK1 promotes ERK2–GAB1 co-immunoprecipitation in cells. Pulldown with bacterially expressed GAB1 domains, purified pERK2 vs non-pERK2, in vitro kinase assay, co-immunoprecipitation with active MEK1 co-transfection The Journal of biological chemistry High 10593929
1999 EGFR phosphorylates recombinant human GAB1 at eight tyrosine residues (Y285, Y373, Y406, Y447, Y472, Y619, Y657, Y689) in vitro; Y657 is the predominant site (50% of incorporated phosphate) and serves as a specific binding site for the SHP2/Syp phosphatase. In vitro kinase assay with purified EGFR, phosphopeptide mapping by 2D-HPLC, Edman degradation, mass spectrometry, GST pulldown with Y657F mutant Biochemistry High 9890893
2000 Insulin receptor kinase phosphorylates human GAB1 in vitro at Y242, Y285, Y373, Y447, Y472, Y619, Y657, Y689; Y447, Y472, and Y619 (NYVPM motifs) account for ~75% of phosphate incorporation and constitute the binding sites for the PI3K p85 regulatory subunit. In vitro kinase assay with purified IR, 2D-HPLC phosphopeptide mapping, MALDI-MS, Edman degradation, GST pulldown with NYVPM site mutants Biochemistry High 10978177
2001 ERK activation by HGF potentiates the GAB1–PI3K association: ERK phosphorylation of the pY-adjacent threonine in the YVPMTP motif increases affinity of GAB1 for the p85 SH2 domain; MEK inhibition reduces HGF-stimulated Gab1/p85 association and Akt activation. MEK inhibitor (U0126), GST pulldown with isolated p85 SH2 domains, phosphopeptide competition (pY vs pYT peptides), co-immunoprecipitation, Akt phosphorylation assay The Journal of biological chemistry High 11445578
2002 EGF-stimulated ERK negatively regulates GAB1 by promoting SHP2-mediated dephosphorylation of GAB1, thereby decreasing GAB1/PI3K association and PI3K/Akt activity—opposite to the positive ERK effect seen with HGF. MEK inhibitor (U0126), co-immunoprecipitation of Gab1/p85, dominant-negative SHP2 overexpression, pervanadate treatment, PI3K/Akt activity assay The Journal of biological chemistry High 11896055
2003 GAB1 recruits SHP2 to dephosphorylate paxillin, causing dissociation of Csk from paxillin/Src complex and Src activation; Gab1 mutant deficient in SHP2 binding (Gab1FF) blocks paxillin–SHP2 complex formation, Src Tyr-530 dephosphorylation, ERK activation, and EGF-induced cell migration. Co-immunoprecipitation, Gab1FF and SHP2-DN expression, Src kinase assay, paxillin phosphorylation assay, cell migration assay The Journal of biological chemistry High 14665621
2004 SHP2 dephosphorylates GAB1 tyrosines within a central YXXP-containing region to prevent RasGAP binding; GAB1 Tyr317 is the principal RasGAP docking site; SHP2-mediated dephosphorylation of this site disengages RasGAP and sustains Ras/ERK activation following EGF stimulation. Substrate trapping (catalytically inactive SHP2), Gab1 YXXP deletion mutants, Tyr→Phe point mutants, RasGAP membrane localization, Ras-GTP assay, SHP2-deficient fibroblasts reconstitution The Journal of biological chemistry High 15574420
2004 ERK1/2 phosphorylates GAB1 at six serine/threonine residues (T312, S381, S454, T476, S581, S597) adjacent to YXXM PI3K-binding motifs; phosphorylation at S454, S581, S597, T476 accounts for ~80% of incorporated phosphate and negatively modulates PI3K/Akt signaling in response to insulin. In vitro ERK1/2 kinase assay, 2D-HPLC phosphopeptide mapping, MALDI-MS, Edman degradation, cellular PI3K and Akt activity assays Biochemistry High 15379552
1999 GAB1 mediates c-Met–induced JNK activation: Met phosphorylates/activates GAB1, which recruits Crk via its SH2 domain; Gab1–Crk complex formation is required for JNK activation and MMP-1 transcription via AP-1 downstream of Met. Co-immunoprecipitation, dominant-negative Crk expression, JNK kinase assay, MMP-1 reporter assay Oncogene High 10618718
2000 Sustained tyrosine phosphorylation of GAB1 by HGF/Met (>1 h vs. transient with EGF) promotes sustained PLCγ recruitment to GAB1 tyrosines Y307, Y373, Y407; a GAB1 mutant lacking these three sites abolishes HGF-induced tubulogenesis while only partially reducing proliferation. 32P-peptide mapping, site-directed mutagenesis (Y307/373/407F), branching tubulogenesis assay, scatter assay Oncogene High 10734310
2001 GAB1 serine/threonine phosphorylation by PKCα and PKCβ1 (activated upon PP1/PP2A inhibition by okadaic acid) causes hypo-tyrosine-phosphorylation of GAB1 and impairs PI3K recruitment, representing a negative regulatory mechanism for HGF/Met signaling. Okadaic acid treatment, PKC isoform-specific inhibitors, co-immunoprecipitation of PI3K/GAB1, biological response assays Oncogene Medium 11313945
2003 GAB1 is required for H2O2-induced JNK activation in fibroblasts via its SHP2-binding site; GAB1 recruits SHP2, PI3K, and Shc upon oxidative stress; SHP2 interaction is pro-apoptotic while PI3K interaction is pro-survival, making GAB1 a dual integrator of cell death vs. survival signals. Gab1−/− MEFs, adenoviral reconstitution with Gab1 point mutants, JNK/ERK/p38 kinase assays, cell viability assay, Src inhibitor PP2 Molecular and cellular biology High 12808090
2005 GAB1 and CXCR4 interact genetically: double CXCR4;Gab1 mutant mice fail to colonize the tongue muscle anlage, whereas each single mutant is sufficient, demonstrating non-redundant cooperative control of muscle progenitor migration. Genetic epistasis (double-mutant mouse analysis), in situ hybridization, ectopic SDF1 chick bead implantation Genes & development High 16166380
2006 Association of GAB1 with SHP2 is a critical event for liver regeneration after partial hepatectomy; liver-specific GAB1 and SHP2 knockouts display identical defects in ERK1/2 activation, immediate-early gene expression, cyclin levels, and hepatocyte proliferation; paradoxically, Akt and IL-6/STAT3 are up-regulated in both KOs. Liver-specific conditional knockouts (LGKO), partial hepatectomy model, ERK/Akt/STAT3 activation assays, gene expression analysis Molecular and cellular biology High 16738330
2005 Liver-specific GAB1 knockout mice show enhanced hepatic insulin sensitivity with elevated IRS-1/IRS-2 tyrosine phosphorylation and Akt activation, but reduced Erk activity and defective IRS-1 Ser612 phosphorylation; GAB1 thus acts as a negative modulator of hepatic insulin signaling through the ERK pathway. Liver-specific GAB1 conditional knockout mice, glucose tolerance tests, insulin signaling phosphorylation assays Nature medicine High 15821749
2007 Knock-in mice reveal effector-specific roles: GAB1–PI3K interaction is essential for EGFR-mediated eyelid closure and keratinocyte migration; GAB1–SHP2 interaction is essential for Met-directed placental development and limb muscle progenitor migration; either direct or indirect GAB1–Met binding is sufficient for muscle precursor migration, but both are required for placenta, liver growth, and palate. Knock-in mice with point mutations in PI3K or SHP2 binding sites and in Grb2/Met-binding site of GAB1 Proceedings of the National Academy of Sciences of the United States of America High 17881575
2008 GAB1 translocation to the plasma membrane requires not only PI3K-derived PIP3 binding by its PH domain but also ERK-dependent phosphorylation of Ser551; inhibiting ERK blocks PH-domain-mediated membrane recruitment of GAB1 even when PI3K is active. MEK/ERK inhibitors, Ser551Ala GAB1 mutant, confocal localization, dominant-active MEK expression Journal of cell science High 19050043
2009 PAK4 is a novel GAB1-interacting protein: HGF induces GAB1–PAK4 association at lamellipodia in a GAB1-phosphorylation-dependent but PAK4-kinase-independent manner; interaction requires proline-rich motifs P4/5 of GAB1 and the GEF-interacting domain of PAK4; GAB1–PAK4 synergize to promote cell dispersal, migration, and invasion; a Gab1 mutant unable to recruit PAK4 fails to promote these responses. Co-immunoprecipitation, pulldown, co-localization by fluorescence microscopy, site-directed mutagenesis of P4/5, siRNA knockdown of PAK4, cell dispersal/invasion assays Molecular and cellular biology High 19289496
2012 GAB1 interacts with the actin regulatory protein cortactin through the SH3 domain of cortactin and the P4/5 proline-rich region of GAB1; this GAB1–cortactin complex is required for Met-driven invadopodia formation and cell invasion; both proteins localize to invadopodia rosettes in Met-transformed cells. Co-immunoprecipitation, SH3 domain pulldown, Gab1-null fibroblasts, siRNA knockdown, structure–function mutagenesis, invadopodia rosette imaging, invasion assay Journal of cell science High 22366451
2012 GAB1 interacts with polarity proteins PAR1 and PAR3: GAB1 binds PAR1 and enhances its kinase activity; GAB1 bridges PAR1 and PAR3 into a transient complex, stimulating PAR3 phosphorylation by PAR1; GAB1 and PAR6 compete for binding to the PAR3 PDZ1 domain; GAB1 depletion causes PAR3 hypophosphorylation, increased PAR3/PAR6 complex formation, accelerated tight junction formation, and lateral domain shortening; GAB1 overexpression disrupts apical-basal polarity and promotes multilumen cyst formation. Co-immunoprecipitation, PAR1 kinase assay, siRNA knockdown, overexpression, confocal microscopy of cyst polarity, transepithelial resistance measurement Molecular cell High 22883624
1998 Insulin receptor kinase phosphorylates GAB1; pGAB1 Tyr472 is the major PI3K-p85 binding site (with Y447 and Y589 contributing); only mutation of Tyr627 abolishes SHP2 binding; the GAB1 PH domain is required for GAB1 tyrosine phosphorylation and SHP2 association in intact cells but not for IR interaction in yeast two-hybrid. Modified yeast two-hybrid with IR kinase, site-directed mutagenesis of tyrosines, co-immunoprecipitation in mammalian cells Molecular endocrinology High 9658397
2003 In cardiomyocytes, LIF/gp130 stimulation induces GAB1 tyrosine phosphorylation and GAB1–SHP2 complex formation; adenoviral overexpression of GAB1 enhances LIF-induced longitudinal elongation of cardiomyocytes via ERK5, whereas a SHP2-binding-defective Gab1(F627/659) mutant abolishes elongation and BNP expression; dominant-negative ERK5 abrogates Gab1-enhanced elongation. Adenoviral Gab1 expression (WT, F627/659 mutant), co-immunoprecipitation, ERK5 kinase assay, cardiomyocyte morphology assay, BNP reporter Circulation research High 12855672
2005 Fluid shear stress induces GAB1 tyrosine phosphorylation, GAB1–p85 PI3K association, and a GAB1–SHP2–PKA–eNOS signalosome; Gab1 Y627F mutation (preventing SHP2 binding) completely abolishes shear-induced eNOS phosphorylation while leaving Akt intact; dominant-negative SHP2 prevents PKA activation and eNOS phosphorylation; flow-induced vasodilation in isolated arteries is blocked by PKA inhibition or YF-Gab1/DN-SHP2 overexpression. Gab1 Y627F adenovirus, dominant-negative SHP2, PKA inhibitor, eNOS/Akt phosphorylation assays, isolated murine carotid artery vasodilation assay Circulation research High 16284184
2016 The non-receptor tyrosine kinase FER phosphorylates GAB1 (and Met Tyr1349) in an HGF- and Met-autophosphorylation-independent manner, leading to specific activation of the SHP2–ERK pathway and promoting ovarian cancer cell motility and in vivo metastasis. FER knockdown (siRNA/shRNA), in vitro kinase assay, phospho-specific Western blot, in vivo metastasis model, co-immunoprecipitation Genes & development High 27401557
2018 A GAB1 missense variant (p.Gly116Glu) in the PH domain causes DFNB26 recessive profound deafness; the dominant suppressor METTL13 (p.Arg544Gln) co-immunoprecipitates with GAB1 and SPRY2, forming at least a tripartite complex; METTL13 modifier allele prevents dysregulation of the HGF/MET/SHP2/SPRY2 pathway in human lymphoblastoid cells. Human genetics, co-immunoprecipitation (GAB1/METTL13/SPRY2), zebrafish morphant rescue with human METTL13 mRNA, MET-signaling gene expression in patient lymphoblastoid cells The Journal of clinical investigation High 29408807
2020 GAB1 is specifically expressed in oligodendrocyte lineage cells and is an effector of PDGF signaling in OPCs; conditional GAB1 deletion in oligodendrocytes causes CNS hypomyelination; GAB1 binds GSK3β and regulates its activity, thereby controlling nuclear β-catenin accumulation and expression of pro-myelination transcription factors. Conditional knockout in OL lineage (Olig2-Cre), co-immunoprecipitation of GAB1 with GSK3β, β-catenin nuclear localization assay, myelination phenotype quantification eLife High 31944179
2015 EGFR-activated Src family kinases (SFKs) maintain GAB1 phosphorylation and GAB1–SHP2 complexes at cytosolic sites distal from EGFR by counteracting repeated GAB1 dephosphorylation; this SFK-dependent mechanism sustains SHP2/ERK signaling beyond EGFR inactivation and is specific to EGFR (not c-MET). SFK inhibitors, co-immunoprecipitation time-courses, computational modeling, pharmacological EGFR/MET inhibitors, phospho-Western analysis Science signaling High 25969544
2019 IL-6-induced MAPK activation is bi-phasic: an early Gab1-independent phase requires SHP2 binding to gp130, followed by a Gab1-dependent amplification phase requiring coordinated recruitment of both Grb2 and SHP2 to Gab1. Gab1 knockout cells, reconstitution with Gab1 point mutants (Grb2- and SHP2-binding sites), kinetic ERK activation assays, gp130 mutant receptors Cell communication and signaling High 31651330
2015 GAB1 mediates cardiac hypertrophic response: cardiac-specific Gab1 knockout mice develop dilated cardiomyopathy under hemodynamic stress (TAC) with severe mitochondrial damage and increased cardiomyocyte apoptosis; loss of Gab1 impairs MAPK signaling and disrupts balance of anti/pro-apoptotic genes. Cardiac-specific conditional KO, TAC model, echocardiography, mitochondrial function assays, MAPK pathway Western blot, gene expression profiling Cell death and differentiation High 26517531
2001 GAB1 links the B-cell antigen receptor to PI3K and SHP2: BCR ligation induces GAB1 tyrosine phosphorylation and translocation from cytosol to plasma membrane, requiring the GAB1 PH domain and PI3K activity; GAB1 overexpression potentiates Akt phosphorylation and SHP2 tyrosine phosphorylation upon BCR stimulation. Overexpression in WEHI-231 B cells, PH domain mutant, PI3K inhibitor (wortmannin), co-immunoprecipitation, confocal microscopy, Akt phosphorylation assay The Journal of biological chemistry High 11278704
2003 GC-GAP, a novel Rho-family GAP, is identified as a GAB1 and GAB2 binding partner by yeast two-hybrid; it displays GAP activity toward RhoA, Rac1, and Cdc42 in vitro; GAB proteins may regulate its cellular localization to control Rac/Cdc42 activity. Yeast two-hybrid screen with Gab2 as bait, in vitro GAP activity assay for Rho-family GTPases, siRNA knockdown, subcellular localization The Journal of biological chemistry Medium 12819203
2014 Gαi1/3 proteins form a complex with KGFR and GAB1 upon KGF stimulation; Gαi1/3 is required upstream of GAB1 recruitment and phosphorylation for PI3K-p85 activation and downstream AKT-mTORC1 signaling in skin keratinocytes. shRNA knockdown of Gαi1/3, co-immunoprecipitation of KGFR/Gαi1/3/Gab1 complex, PI3K activity assay, Akt/mTORC1 phosphorylation assays, cell proliferation/migration assays The Journal of investigative dermatology High 25078664
2015 Gαi1/3 interact with CD14 and GAB1 in LPS-stimulated macrophages; this CD14–Gαi1/3–GAB1 complex is required for PI3K-Akt activation; Gαi1/3 deficiency decreases TLR4 endocytosis, IRF3 phosphorylation, and macrophage M1 polarization, promoting LPS tolerance. Co-immunoprecipitation of CD14/Gαi1/3/Gab1, shRNA knockdown of Gαi1/3 in BMDMs, PI3K/Akt activation assays, in vivo LPS tolerance model Proceedings of the National Academy of Sciences of the United States of America High 25825741
2011 Endothelium-specific GAB1 knockout mice show impaired blood flow recovery after hindlimb ischemia; in endothelial cells, HGF induces GAB1–SHP2 complex required for migration/proliferation via ERK1/2 and ERK5, and GAB1–p85 complex required for partial migration via Akt; VEGF gene transfer rescues flow recovery in Gab1ECKO mice whereas HGF does not. Endothelium-specific conditional KO, hindlimb ischemia model, co-immunoprecipitation, ERK1/2/ERK5/Akt assays, gene transfer rescue experiment Circulation research High 21293003
2012 Cancer-associated GAB1 T387N mutation abrogates a negative-feedback phosphorylation site mapped by mass spectrometry; T387 is phosphorylated transiently by EGF and sustained by HGF, and its mutation to Asn enhances ERK signaling and aberrant branching morphogenesis in mammary epithelial cells. Mass spectrometry phosphosite mapping, site-directed mutagenesis, 3D Matrigel culture, ERK activation assay Oncogene High 22751113

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis. Nature 500 8906793
2000 Coupling of Gab1 to c-Met, Grb2, and Shp2 mediates biological responses. The Journal of cell biology 295 10871282
2000 Essential role of Gab1 for signaling by the c-Met receptor in vivo. The Journal of cell biology 214 10995442
1999 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. Molecular and cellular biology 172 10022866
2004 A novel role for Gab1 and SHP2 in epidermal growth factor-induced Ras activation. The Journal of biological chemistry 167 15574420
2004 Noonan syndrome-associated SHP2/PTPN11 mutants cause EGF-dependent prolonged GAB1 binding and sustained ERK2/MAPK1 activation. Human mutation 158 14974085
2005 CXCR4 and Gab1 cooperate to control the development of migrating muscle progenitor cells. Genes & development 157 16166380
1997 Association of the multisubstrate docking protein Gab1 with the hepatocyte growth factor receptor requires a functional Grb2 binding site involving tyrosine 1356. The Journal of biological chemistry 153 9252406
2000 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. The Journal of biological chemistry 147 10913131
2003 Roles of Gab1 and SHP2 in paxillin tyrosine dephosphorylation and Src activation in response to epidermal growth factor. The Journal of biological chemistry 145 14665621
2001 Phosphotyrosines 627 and 659 of Gab1 constitute a bisphosphoryl tyrosine-based activation motif (BTAM) conferring binding and activation of SHP2. The Journal of biological chemistry 145 11323411
2000 Sustained recruitment of phospholipase C-gamma to Gab1 is required for HGF-induced branching tubulogenesis. Oncogene 136 10734310
2020 LncRNA TUG1 alleviates sepsis-induced acute lung injury by targeting miR-34b-5p/GAB1. BMC pulmonary medicine 135 32087725
2014 miR-150 influences B-cell receptor signaling in chronic lymphocytic leukemia by regulating expression of GAB1 and FOXP1. Blood 132 24787006
2002 ERK negatively regulates the epidermal growth factor-mediated interaction of Gab1 and the phosphatidylinositol 3-kinase. The Journal of biological chemistry 121 11896055
1997 Gab1 coupling to the HGF/Met receptor multifunctional docking site requires binding of Grb2 and correlates with the transforming potential. Oncogene 116 9444958
2014 Requirement of Gαi1/3-Gab1 signaling complex for keratinocyte growth factor-induced PI3K-AKT-mTORC1 activation. The Journal of investigative dermatology 109 25078664
1997 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. The Journal of biological chemistry 104 9242692
2000 Dominant modifier DFNM1 suppresses recessive deafness DFNB26. Nature genetics 101 11101839
2006 Concerted functions of Gab1 and Shp2 in liver regeneration and hepatoprotection. Molecular and cellular biology 98 16738330
2001 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 88 11314042
2006 Reduced phosphatase activity of SHP-2 in LEOPARD syndrome: consequences for PI3K binding on Gab1. FEBS letters 85 16638574
1999 Engagement of Gab1 and Gab2 in erythropoietin signaling. The Journal of biological chemistry 84 10455108
2003 Activation of gp130 transduces hypertrophic signal through interaction of scaffolding/docking protein Gab1 with tyrosine phosphatase SHP2 in cardiomyocytes. Circulation research 80 12855672
2005 Gab1, SHP2, and protein kinase A are crucial for the activation of the endothelial NO synthase by fluid shear stress. Circulation research 75 16284184
2002 Gab1 and SHP-2 promote Ras/MAPK regulation of epidermal growth and differentiation. The Journal of cell biology 75 12370245
1999 Met-induced JNK activation is mediated by the adapter protein Crk and correlates with the Gab1 - Crk signaling complex formation. Oncogene 74 10618718
1999 A conserved inositol phospholipid binding site within the pleckstrin homology domain of the Gab1 docking protein is required for epithelial morphogenesis. The Journal of biological chemistry 73 10531383
2009 Pak4, a novel Gab1 binding partner, modulates cell migration and invasion by the Met receptor. Molecular and cellular biology 69 19289496
2015 MicroRNA-409-3p suppresses colorectal cancer invasion and metastasis partly by targeting GAB1 expression. International journal of cancer 68 25991585
2005 Deletion of Gab1 in the liver leads to enhanced glucose tolerance and improved hepatic insulin action. Nature medicine 68 15821749
2005 Participation of both Gab1 and Gab2 in the activation of the ERK/MAPK pathway by epidermal growth factor. The Biochemical journal 64 15952937
1999 Gab1 mediates neurite outgrowth, DNA synthesis, and survival in PC12 cells. The Journal of biological chemistry 64 10601297
2003 Gab1 is required for EGF receptor signaling and the transformation by activated ErbB2. Oncogene 62 12629518
1998 Determination of Gab1 (Grb2-associated binder-1) interaction with insulin receptor-signaling molecules. Molecular endocrinology (Baltimore, Md.) 61 9658397
2004 Distinct domains in the SHP-2 phosphatase differentially regulate epidermal growth factor receptor/NF-kappaB activation through Gab1 in glioblastoma cells. Molecular and cellular biology 60 14701753
2012 Met receptor tyrosine kinase signals through a cortactin-Gab1 scaffold complex, to mediate invadopodia. Journal of cell science 57 22366451
2007 Distinct requirements for Gab1 in Met and EGF receptor signaling in vivo. Proceedings of the National Academy of Sciences of the United States of America 54 17881575
2017 Increased levels of Gab1 and Gab2 adaptor proteins skew interleukin-4 (IL-4) signaling toward M2 macrophage-driven pulmonary fibrosis in mice. The Journal of biological chemistry 53 28687632
2015 EGF augments TGFβ-induced epithelial-mesenchymal transition by promoting SHP2 binding to GAB1. Journal of cell science 52 26359300
2000 A switch from p130Cas/Crk to Gab1/Crk signaling correlates with anchorage independent growth and JNK activation in cells transformed by the Met receptor oncoprotein. Oncogene 52 11146548
2008 A new mechanism for the regulation of Gab1 recruitment to the plasma membrane. Journal of cell science 51 19050043
2015 Gαi1 and Gαi3 regulate macrophage polarization by forming a complex containing CD14 and Gab1. Proceedings of the National Academy of Sciences of the United States of America 50 25825741
2003 Gab1 is an integrator of cell death versus cell survival signals in oxidative stress. Molecular and cellular biology 50 12808090
2002 Distinct recruitment and function of Gab1 and Gab2 in Met receptor-mediated epithelial morphogenesis. Molecular biology of the cell 50 12058075
2001 The Gab1 docking protein links the b cell antigen receptor to the phosphatidylinositol 3-kinase/Akt signaling pathway and to the SHP2 tyrosine phosphatase. The Journal of biological chemistry 50 11278704
2015 Gab1 and Mapk Signaling Are Essential in the Hair Cycle and Hair Follicle Stem Cell Quiescence. Cell reports 49 26456821
2011 Docking protein Gab1 is an essential component of postnatal angiogenesis after ischemia via HGF/c-met signaling. Circulation research 49 21293003
2001 ERK regulates the hepatocyte growth factor-mediated interaction of Gab1 and the phosphatidylinositol 3-kinase. The Journal of biological chemistry 48 11445578
1999 Identification of tyrosine phosphorylation sites in human Gab-1 protein by EGF receptor kinase in vitro. Biochemistry 47 9890893
2004 Identification of major ERK-related phosphorylation sites in Gab1. Biochemistry 46 15379552
2016 HGF-independent regulation of MET and GAB1 by nonreceptor tyrosine kinase FER potentiates metastasis in ovarian cancer. Genes & development 45 27401557
2016 MicroRNA-150 suppresses cell proliferation and metastasis in hepatocellular carcinoma by inhibiting the GAB1-ERK axis. Oncotarget 43 26871477
2001 ShcA and Grb2 mediate polyoma middle T antigen-induced endothelial transformation and Gab1 tyrosine phosphorylation. The EMBO journal 43 11707404
2003 GC-GAP, a Rho family GTPase-activating protein that interacts with signaling adapters Gab1 and Gab2. The Journal of biological chemistry 42 12819203
2005 Resveratrol inhibits angiotensin II- and epidermal growth factor-mediated Akt activation: role of Gab1 and Shp2. Molecular pharmacology 40 15849355
2001 Gab1 phosphorylation: a novel mechanism for negative regulation of HGF receptor signaling. Oncogene 40 11313945
2004 Gab1 contributes to cytoskeletal reorganization and chemotaxis in response to platelet-derived growth factor. The Journal of biological chemistry 37 14973141
2017 miR-141-3p inhibits fibroblast proliferation and migration by targeting GAB1 in keloids. Biochemical and biophysical research communications 36 28619509
2014 Essential roles of Gab1 tyrosine phosphorylation in growth factor-mediated signaling and angiogenesis. International journal of cardiology 36 25528308
2009 Non-redundant roles of the Gab1 and Gab2 scaffolding adapters in VEGF-mediated signalling, migration, and survival of endothelial cells. Cellular signalling 36 19233262
2000 Identification of major tyrosine phosphorylation sites in the human insulin receptor substrate Gab-1 by insulin receptor kinase in vitro. Biochemistry 36 10978177
2020 Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination. eLife 35 31944179
2015 Cardiac Gab1 deletion leads to dilated cardiomyopathy associated with mitochondrial damage and cardiomyocyte apoptosis. Cell death and differentiation 35 26517531
2007 Hepatocyte growth factor induces glucose uptake in 3T3-L1 adipocytes through A Gab1/phosphatidylinositol 3-kinase/Glut4 pathway. The Journal of biological chemistry 35 17284447
2009 A role for Gab1/SHP2 in thrombin activation of PAK1: gene transfer of kinase-dead PAK1 inhibits injury-induced restenosis. Circulation research 34 19359598
2018 Modifier variant of METTL13 suppresses human GAB1-associated profound deafness. The Journal of clinical investigation 33 29408807
2017 MAPK pathway inhibition induces MET and GAB1 levels, priming BRAF mutant melanoma for rescue by hepatocyte growth factor. Oncotarget 33 28147313
2012 Alpha-synuclein elicits glucose uptake and utilization in adipocytes through the Gab1/PI3K/Akt transduction pathway. Cellular and molecular life sciences : CMLS 33 23124190
2006 Gab1 is required for cell cycle transition, cell proliferation, and transformation induced by an oncogenic met receptor. Molecular biology of the cell 33 16775003
2006 Bisindolylmaleimide I suppresses fibroblast growth factor-mediated activation of Erk MAP kinase in chondrocytes by preventing Shp2 association with the Frs2 and Gab1 adaptor proteins. The Journal of biological chemistry 32 17145761
2005 Host adaptor proteins Gab1 and CrkII promote InlB-dependent entry of Listeria monocytogenes. Cellular microbiology 32 15679846
1999 Activated ERK2 interacts with and phosphorylates the docking protein GAB1. The Journal of biological chemistry 32 10593929
2021 FoxO1-GAB1 axis regulates homing capacity and tonic AKT activity in chronic lymphocytic leukemia. Blood 31 33786575
2013 Computational Model of Gab1/2-Dependent VEGFR2 Pathway to Akt Activation. PloS one 31 23805312
2019 Inhibition of microRNA-29a alleviates hyperoxia-induced bronchopulmonary dysplasia in neonatal mice via upregulation of GAB1. Molecular medicine (Cambridge, Mass.) 30 31892308
2018 MicroRNA-29a-3p Downregulation Causes Gab1 Upregulation to Promote Glioma Cell Proliferation. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 29 30016785
2017 Role of GAB1/PI3K/AKT signaling high glucose-induced cardiomyocyte apoptosis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 29 28738535
2012 Functional characterization of cancer-associated Gab1 mutations. Oncogene 29 22751113
2012 The signaling adaptor GAB1 regulates cell polarity by acting as a PAR protein scaffold. Molecular cell 29 22883624
2007 Coupling of Grb2 to Gab1 mediates hepatocyte growth factor-induced high intensity ERK signal required for inhibition of HepG2 hepatoma cell proliferation. The Journal of biological chemistry 29 18003605
2000 The osmotic shock-induced glucose transport pathway in 3T3-L1 adipocytes is mediated by gab-1 and requires Gab-1-associated phosphatidylinositol 3-kinase activity for full activation. The Journal of biological chemistry 29 10842168
2021 Circ_0061012 contributes to IL-22-induced proliferation, migration and invasion in keratinocytes through miR-194-5p/GAB1 axis in psoriasis. Bioscience reports 28 33393621
2015 EGFR-activated Src family kinases maintain GAB1-SHP2 complexes distal from EGFR. Science signaling 28 25969544
2013 Down-regulation of Gab1 inhibits cell proliferation and migration in hilar cholangiocarcinoma. PloS one 28 24312291
2005 Alternate paths from epidermal growth factor receptor to Akt in malignant versus nontransformed lung epithelial cells: ErbB3 versus Gab1. American journal of respiratory cell and molecular biology 28 16055672
2001 Role of phosphatidylinositol-3 kinase and its association with Gab1 in thrombopoietin-mediated up-regulation of platelet function. Experimental hematology 28 11376875
2016 Targeted nanoconjugate co-delivering siRNA and tyrosine kinase inhibitor to KRAS mutant NSCLC dissociates GAB1-SHP2 post oncogene knockdown. Scientific reports 27 27530552
2020 Human Cytomegalovirus miR-US5-2 Downregulation of GAB1 Regulates Cellular Proliferation and UL138 Expression through Modulation of Epidermal Growth Factor Receptor Signaling Pathways. mSphere 26 32759334
2017 MicroRNA-200a Suppresses Cell Invasion and Migration by Directly Targeting GAB1 in Hepatocellular Carcinoma. Oncology research 26 28081727
2016 Gab1 adaptor protein acts as a gatekeeper to balance hepatocyte death and proliferation during acetaminophen-induced liver injury in mice. Hepatology (Baltimore, Md.) 26 26680679
2004 Biochemical and biological responses induced by coupling of Gab1 to phosphatidylinositol 3-kinase in RET-expressing cells. Biochemical and biophysical research communications 26 15351743
2003 Gab1, SHP-2 and other novel regulators of Ras: targets for anticancer drug discovery? Current cancer drug targets 26 12769687
2019 The multi-site docking protein Grb2-associated binder 1 (Gab1) enhances interleukin-6-induced MAPK-pathway activation in an SHP2-, Grb2-, and time-dependent manner. Cell communication and signaling : CCS 25 31651330
2018 MicroRNA-590-5p suppresses the proliferation and invasion of non-small cell lung cancer by regulating GAB1. European review for medical and pharmacological sciences 25 30280777
2006 GRB2-mediated recruitment of GAB2, but not GAB1, to SF-STK supports the expansion of Friend virus-infected erythroid progenitor cells. Oncogene 25 16314834
2012 Participation of Gab1 and Gab2 in IL-22-mediated keratinocyte proliferation, migration, and differentiation. Molecular and cellular biochemistry 24 22851227
2003 Epidermal growth factor receptor-dependent activation of Gab1 is involved in ErbB-2-mediated mammary tumor progression. Oncogene 24 14668796
2020 Metformin reduces HGF-induced resistance to alectinib via the inhibition of Gab1. Cell death & disease 23 32041944
2008 Interaction of scaffolding adaptor protein Gab1 with tyrosine phosphatase SHP2 negatively regulates IGF-I-dependent myogenic differentiation via the ERK1/2 signaling pathway. The Journal of biological chemistry 23 18577518