Affinage

GAB2

GRB2-associated-binding protein 2 · UniProt Q9UQC2

Length
676 aa
Mass
74.5 kDa
Annotated
2026-04-28
100 papers in source corpus 41 papers cited in narrative 41 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GAB2 is a multi-site docking/scaffolding protein that amplifies PI3K/AKT and SHP2/Ras/ERK signaling downstream of receptor tyrosine kinases, cytokine receptors, antigen receptors, and oncoproteins by recruiting SH2-domain effectors—principally the p85 subunit of PI3K, SHP2, GRB2, PLCγ2, and CrkL—to specific phosphotyrosine motifs upon phosphorylation by kinases including Src, ZAP-70, Jak2, and Lyn (PMID:9885561, PMID:11334882, PMID:12464621, PMID:18644434). GAB2 is negatively regulated through AKT-mediated Ser159 phosphorylation, RSK-mediated phosphorylation that uncouples SHP2, and 14-3-3 recruitment to phospho-Ser210/Thr391 that dissociates GAB2 from GRB2–receptor complexes, establishing multiple feedback loops that restrain its signaling output (PMID:11782427, PMID:19172738, PMID:23401857). Genetic ablation of GAB2 in mice reveals essential, non-redundant roles in mast cell degranulation via PI3K/ARF1 (PMID:11449275, PMID:21653832), osteoclastogenesis via RANK–NF-κB/Akt/JNK and PLCγ2/NFATc1 (PMID:15750601, PMID:17053833), Fcγ receptor–mediated phagocytosis (PMID:12821647), M2 macrophage polarization via STAT6 (PMID:28687632), endothelial thromboinflammation via the CBM signalosome (PMID:35895897), and BCR-ABL–driven myeloid and lymphoid leukemogenesis through distinct PI3K- and SHP2-dependent pathways (PMID:12124177, PMID:26773044). GAB2 also promotes tumor cell migration and invasion by SHP2-dependent suppression of RhoA through p190A RhoGAP and Vav2 (PMID:21118992), and cooperates with ErbB2/Neu in mammary carcinogenesis and metastasis (PMID:16369543, PMID:17310989).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    Identification of GAB2 as a cytokine-responsive scaffolding protein that recruits SHP2 and PI3K resolved how Dos/Gab-family docking proteins diversify downstream signaling from receptor complexes, revealing a novel SHP2-dependent pathway to immediate-early gene activation distinct from classical MAPK signaling.

    Evidence Cloning, dominant-negative mutant expression, reporter gene assays, and co-immunoprecipitation in cytokine-stimulated cells

    PMID:9885561

    Open questions at the time
    • Identity of upstream kinase(s) phosphorylating GAB2 not determined
    • Physiological role in vivo not established
  2. 2001 High

    Mapping of specific GAB2 phosphotyrosine residues to distinct SH2 partners (Y452/Y476/Y584 for PI3K p85; Y614 for SHP2; Y266/Y293 for CrkL) established GAB2 as a modular signaling platform where individual phosphosites independently recruit effectors, and genetic ablation in mice revealed that GAB2 is the principal PI3K activator downstream of FcεRI, essential for mast cell degranulation and anaphylaxis.

    Evidence Modified yeast two-hybrid with Lyn kinase and tyrosine mutants; Gab2 knockout mice with mast cell functional assays and anaphylaxis models

    PMID:11334882 PMID:11449275

    Open questions at the time
    • Structural basis of phosphosite–SH2 domain selectivity not resolved
    • Redundancy with GAB1 in mast cells not fully assessed
  3. 2001 High

    Demonstration that GAB2–SHP2 interaction is required for M-CSF-driven macrophage differentiation and that GAB2 inhibits TCR-mediated NF-AT activation via SHP2 and PI3K extended GAB2 function beyond growth factor signaling to lineage specification and T cell inhibition.

    Evidence SHP2-binding-defective GAB2 mutants in macrophage differentiation; GAB2 domain mutants, ZAP-70 kinase assays, and NF-AT reporter assays in T cells; transgenic and KO mice

    PMID:11287610 PMID:11572860 PMID:12640133

    Open questions at the time
    • How GAB2 switches between activating (macrophage) and inhibitory (T cell) outputs not resolved
    • Quantitative contribution of Gads vs GRB2 in T cell recruitment unclear
  4. 2002 High

    Identification of GAB2 as an essential mediator of BCR-ABL leukemogenesis—recruited via GRB2 to BCR-ABL pY177 to activate PI3K/Akt and Ras/ERK—and of negative feedback from AKT via Ser159 phosphorylation that restrains GAB2 tyrosine phosphorylation and transforming activity established GAB2 as both a critical oncogenic intermediary and a regulated signaling node.

    Evidence Gab2 KO bone marrow transformation by BCR-ABL, BCR-ABL Y177F mutant; in vitro AKT kinase assay on Ser159, S159A mutant with enhanced transformation

    PMID:11782427 PMID:12124177

    Open questions at the time
    • Relative contributions of PI3K vs SHP2 arms to myeloid vs lymphoid BCR-ABL transformation not yet distinguished
    • Structural basis of Ser159-mediated inhibition unknown
  5. 2002 High

    Establishing that Src constitutively associates with GAB2 and is required for EGF-induced PI3K/Akt activation, and that GAB2 PH domain–dependent recruitment to nascent phagosomes amplifies PI3K signaling for FcγR-mediated phagocytosis, broadened the upstream kinase repertoire and defined a spatially restricted scaffolding role at membrane compartments.

    Evidence Src inhibitor PP1, Csk KO cells, in vitro phosphorylation; Gab2 KO macrophages, confocal imaging of phagosome recruitment, PH domain mutants

    PMID:12464621 PMID:12821647

    Open questions at the time
    • Lipid species binding the PH domain in phagosomes not identified
    • Whether GAB2 PH domain localization is PI(3,4,5)P3-specific not confirmed
  6. 2005 High

    Demonstration that GAB2 mediates RANK-induced NF-κB/Akt/JNK activation and that Gab2 KO mice develop osteopetrosis, alongside evidence that GAB2 cooperates with ErbB2/Neu in breast carcinogenesis via SHP2-ERK, established GAB2 as essential for osteoclastogenesis and a driver of solid tumor progression.

    Evidence Gab2 KO mice bone histomorphometry and osteoclast assays; Gab2 KO crossed with Neu transgenic, 3D culture, domain mutants

    PMID:15750601 PMID:16369543

    Open questions at the time
    • Direct RANK–GAB2 binding interface not structurally characterized
    • Whether GAB2 functions in osteoblasts is unknown
  7. 2006 High

    PLCγ2 was found to complex with GAB2 and modulate its phosphorylation during RANKL-stimulated osteoclastogenesis, and GAB2 via SHP2 was shown to activate Rac/JNK for Kit-evoked mast cell proliferation, revealing cell-type-specific effector partnerships that diversify GAB2 output.

    Evidence PLCγ2 KO mice and co-IP of PLCγ2–GAB2; compound Gab2 KO/Kit mutant mice, SHP2-binding-defective GAB2 rescue, Rac/JNK assays

    PMID:16873377 PMID:17053833

    Open questions at the time
    • Whether PLCγ2–GAB2 interaction is direct or bridged by phosphotyrosine motifs not established
    • GAB2 role in non-mast cell Kit signaling (e.g., melanocytes, ICCs) unexplored
  8. 2008 High

    Discovery that 14-3-3 recruitment to phospho-Ser210/Thr391 dissociates GAB2 from GRB2/receptor complexes to terminate signaling, and that Jak2 directly phosphorylates GAB2 Tyr643 to promote SHP2 binding and ERK activation, defined a second negative regulatory mechanism and a new upstream kinase.

    Evidence S210A/T391A double mutant with sustained signaling and transformation; constitutive 14-3-3 binding site insertion; in vitro Jak2 kinase assay on GAB2, Y643F mutagenesis

    PMID:18644434 PMID:19172738

    Open questions at the time
    • Kinase(s) responsible for Ser210/Thr391 phosphorylation in vivo not identified
    • Whether 14-3-3 binding affects GAB2 subcellular localization not determined
  9. 2009 High

    Crystal structures of GAB2 peptides complexed with the GRB2 C-SH3 domain revealed two distinct binding modes (PPII helix vs 3₁₀ helix) for the RxxK motif, providing the first atomic-resolution view of GAB2–effector recognition.

    Evidence X-ray crystallography, isothermal titration calorimetry, peptide arrays

    PMID:19523899

    Open questions at the time
    • No full-length or larger-fragment GAB2 structure exists
    • Whether both SH3 sites are simultaneously occupied in cells unknown
  10. 2010 High

    GAB2 was shown to promote cell migration by SHP2-dependent activation of Vav2 and plasma membrane recruitment of p190A RhoGAP, suppressing RhoA and reducing stress fibers, providing the first mechanistic link from GAB2 to Rho GTPase regulation and cytoskeletal remodeling.

    Evidence GAB2 ΔShp2 mutants, RhoA activity assays, p190A RhoGAP knockdown, constitutively active RhoA rescue in mammary epithelial cells

    PMID:21118992

    Open questions at the time
    • Direct SHP2 substrate(s) mediating Vav2 phosphorylation not identified
    • In vivo relevance of Gab2–RhoA axis in metastasis not tested
  11. 2011 High

    Knock-in mice with PI3K- or SHP2-binding site mutations in GAB2 dissected effector-specific outputs in mast cells, showing PI3K is required for ARF1-dependent granule translocation while both PI3K and SHP2 sites are needed for degranulation and anaphylaxis, establishing the first genetically separated effector arms in vivo.

    Evidence Gab2 knock-in mice (PI3K-binding and SHP2-binding site mutations), ARF1 activation assays, granule translocation imaging, anaphylaxis models

    PMID:21653832

    Open questions at the time
    • GEF linking PI3K to ARF1 downstream of GAB2 not identified
    • Whether ARF1 pathway operates in non-mast cell GAB2-expressing contexts unknown
  12. 2013 High

    RSK was identified as a third negative-feedback kinase phosphorylating GAB2 on conserved residues to inhibit SHP2 recruitment without affecting GRB2 binding, selectively restricting GAB2-SHP2-dependent cell motility, revealing pathway-selective feedback regulation.

    Evidence In vitro RSK kinase assay, mass spectrometry, site-directed mutagenesis, co-IP, migration/invasion assays

    PMID:23401857

    Open questions at the time
    • Identity of the specific RSK-phosphorylated residues that block SHP2 SH2 binding not structurally explained
    • In vivo validation of RSK–GAB2 feedback in tumors not reported
  13. 2016 High

    Genetic epistasis in BCR-ABL leukemia models demonstrated that myeloid (CML) transformation requires both GAB2–PI3K and GAB2–SHP2 arms, while lymphoid (B-ALL) transformation depends primarily on GAB2–SHP2, providing lineage-specific pathway assignments within a single oncogene system.

    Evidence Gab2 KO mice with BCR-ABL1 transduction, domain-specific mutant rescue in CML and B-ALL models

    PMID:26773044

    Open questions at the time
    • Why lymphoid transformation is SHP2-dependent but PI3K-independent not mechanistically explained
    • Whether these distinctions hold in human CML/B-ALL not confirmed
  14. 2017 High

    GAB2 was found to have non-redundant roles with GAB1 in macrophage polarization—GAB2 activates STAT6 for M2 polarization while GAB1 activates AKT—and was placed downstream of YAP/TAZ transcriptional regulation in endometrial cancer, integrating GAB2 into Hippo pathway cross-talk.

    Evidence Gab2 KO and Gab1 conditional KO mice, IL-4/STAT6 signaling, bleomycin fibrosis model; YAP/TAZ siRNA with GAB2 protein and PI3K readouts in endometrial cancer cells

    PMID:28202507 PMID:28687632

    Open questions at the time
    • Direct mechanism of GAB2-dependent STAT6 activation not resolved
    • Whether YAP/TAZ directly bind GAB2 promoter not shown
  15. 2022 High

    GAB2 was discovered to facilitate assembly of the CARMA3–BCL10–MALT1 (CBM) signalosome in endothelial cells, mediating IL-1β-induced Rho activation, NF-κB-dependent tissue factor expression, P-selectin/VWF exocytosis, and venous thrombosis, extending GAB2 function to endothelial thromboinflammation.

    Evidence Gab2 silencing, MALT1 inhibitor mepazine, IVC ligation thrombosis model, P-selectin/VWF exocytosis assays, NF-κB signaling

    PMID:35895897

    Open questions at the time
    • How GAB2 physically connects to MALT1/CBM complex not defined
    • Whether GAB2 scaffolding of CBM occurs in non-endothelial cell types unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length structural model of GAB2 and the mechanism by which its intrinsically disordered regions coordinate simultaneous effector binding remain unknown; the GEF connecting GAB2–PI3K to ARF1, the structural basis of 14-3-3/RSK-mediated negative regulation, and the in vivo significance of GAB2 in neurodegeneration are also unresolved.
  • No full-length GAB2 structure
  • GEF for PI3K-ARF1 link unidentified
  • Neurodegeneration role based on single siRNA study

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0098772 molecular function regulator activity 3
Localization
GO:0005829 cytosol 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 9 R-HSA-168256 Immune System 7 R-HSA-1643685 Disease 5 R-HSA-1266738 Developmental Biology 2 R-HSA-5357801 Programmed Cell Death 1
Partners
CRKLGRB2JAK2LYNPIK3R1PLCG2SHP2SRC
Complex memberships
CBM signalosome (CARMA3-BCL10-MALT1)GRB2/GAB2 complex

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 GAB2 (p97) is a scaffolding protein that, upon cytokine, growth factor, or antigen receptor stimulation, becomes tyrosyl phosphorylated and associates with SH2 domain-containing proteins including SHP2 and PI3K. Expression of p97 mutants unable to bind SHP2 blocks cytokine-induced c-fos promoter activation, inhibiting Elk1-mediated and STAT5-mediated transactivation, without inhibiting MAPK activation, revealing a novel pathway to immediate-early gene activation. Cloning, dominant-negative mutant expression, reporter gene assays, co-immunoprecipitation Molecular cell High 9885561
1999 GAB2 contains a pleckstrin homology (PH) domain and, upon tyrosine phosphorylation, physically interacts with SHP2 and GRB2. GAB2 has an inhibitory effect on Elk-1-dependent transcription triggered by oncogenic Ras or growth factors, while having a similar function to GAB1 in ERK activation, indicating distinct roles in cytoplasmic-nuclear signal transduction. Co-immunoprecipitation, reporter gene assays, overexpression with dominant-active Ras The Journal of biological chemistry High 10391903
2001 GAB2-deficient mast cells have defective responses to FcεRI stimulation (degranulation and cytokine gene expression), and GAB2 is the principal activator of PI3K in response to FcεRI activation, establishing that Dos/Gab family scaffolds regulate the PI3K pathway in vivo. Gab2 knockout mice, mast cell functional assays, passive cutaneous and systemic anaphylaxis models, biochemical signaling analysis Nature High 11449275
2001 GAB2 associates with GRB2, SHP2, p85 subunit of PI3K, SHIP, and SHC downstream of the M-CSF receptor (Fms). Overexpression of GAB2 enhanced MAPK activity and macrophage differentiation but reduced proliferation, while a Gab2 mutant unable to bind SHP2 failed to potentiate MAPK activity and inhibited macrophage differentiation, demonstrating that GAB2-SHP2 interaction is essential for the M-CSF differentiation signal. Co-immunoprecipitation, overexpression of wild-type and SHP2-binding-defective Gab2 mutants, MAPK kinase assays, cell differentiation assays Molecular and cellular biology High 11287610
2001 GAB2 is phosphorylated by ZAP-70 and co-precipitates with ZAP-70, LAT, and CD3ζ upon TCR stimulation. Overexpression of GAB2 inhibits NF-AT activation and IL-2 production; this inhibitory function requires SHP2-binding sites and the PH domain of GAB2, and depends on PI3K recruitment. GAB2 functions as a switch molecule toward inhibition of TCR signal transduction by recruiting inhibitory molecules. Co-immunoprecipitation, kinase assays, reporter gene assays (NF-AT, IL-2), Gab2 domain mutants The Journal of biological chemistry High 11572860
2002 BCR/ABL recruits GAB2 via a GRB2/GAB2 complex through BCR/ABL phosphotyrosine 177. GAB2 mediates BCR/ABL-driven PI3K/Akt and Ras/Erk activation; Gab2-deficient mouse bone marrow myeloid progenitors are resistant to transformation by BCR/ABL, identifying GAB2 as a key determinant of BCR/ABL leukemogenesis. Gab2 knockout mouse bone marrow transformation assays, Co-immunoprecipitation, signaling pathway analysis, BCR/ABL-Y177F mutant Cancer cell High 12124177
2002 PKB/AKT constitutively associates with GAB2, phosphorylates GAB2 on Ser159 in vitro, and this phosphorylation inhibits GAB2 tyrosine phosphorylation (negative feedback). The Gab2-S159A mutant enhances heregulin-induced GAB2 tyrosine phosphorylation, amplifies ERK and PKB pathway activation, and exhibits potent transforming activity, establishing a negative-feedback loop from PI3K/PKB to GAB2. In vitro kinase assay, site-directed mutagenesis (S159A), co-immunoprecipitation, transformation assay, signaling assays The EMBO journal High 11782427
2002 GAB2 is required for Fc gamma receptor (FcγR)-initiated phagocytosis in macrophages. Upon FcγR activation, GAB2 becomes tyrosyl phosphorylated and associates with p85 and SHP-2; GAB2 is recruited to the nascent phagosome via its PH domain (requiring PI3K lipid products and facilitated by GRB2 binding), where it amplifies PI3K/Akt signaling required for phagocytosis. Gab2 knockout macrophages, phagocytosis assays, confocal fluorescence microscopy, co-immunoprecipitation, wortmannin treatment, domain mutants The Journal of cell biology High 12821647
2002 GAB2 mediates Src phosphorylation downstream of EGF receptor signaling; Src constitutively associates with GAB2 via its SH3 domain interacting with GAB2 proline-rich sequences. Src-dependent GAB2 phosphorylation is required for EGF-induced PI3K/Akt activation and DNA synthesis in hepatocytes. Gab2 mutants with SHP2-binding-site deletions increase EGF-induced GAB2 phosphorylation and PI3K activity but block MAPK activation, demonstrating SHP2-mediated downregulation of GAB2. Src inhibitor PP1, Csk knockout cells, in vitro phosphorylation, co-immunoprecipitation, GAB2 mutants, DNA synthesis assays The Journal of biological chemistry High 12464621
2003 GAB2 interacts with GC-GAP, a novel Rho family GTPase-activating protein with activity toward RhoA, Rac1, and Cdc42, linking GAB2 scaffolding function to Rho GTPase regulation. Yeast two-hybrid screen, co-immunoprecipitation, in vitro GAP activity assay, siRNA knockdown The Journal of biological chemistry Medium 12819203
2003 GAB2 interaction with LAT upon TCR stimulation requires the c-Met binding domain (MBD) of GAB2 and a novel PXXXR Grb2/Gads SH3 binding motif. Through constitutive association with Gads/Grb2, GAB2 is recruited to lipid rafts after TCR ligation to exert its inhibitory function. Transgenic mice expressing wild-type GAB2 show impaired T cell responses, while Gab2-deficient mice show enhanced proliferative responses. Co-immunoprecipitation, GAB2 domain mutants, transgenic mice, Gab2-deficient mice, lipid raft fractionation Molecular and cellular biology High 12640133
2001 Specific tyrosine residues on GAB2 mediate binding to distinct SH2-domain proteins: Y452, Y476, and Y584 mediate PI3K p85 binding; Y614 mediates SHP-2 binding; and Y266 and Y293 mediate CrkL SH2 binding, as established in a modified yeast two-hybrid system with inducible Lyn kinase. Modified yeast two-hybrid with inducible Lyn kinase, tyrosine mutants of GAB2 FEBS letters Medium 11334882
2004 In IL-2-stimulated T lymphocytes, SHP-2 binds tyrosine residues Y614 (via N-terminal SH2) and Y643 (via C-terminal SH2) of GAB2. Mutation of Y614 alone is sufficient to prevent SHP-2 recruitment, and this blocks ERK activation and c-fos SRE transcription, demonstrating that GAB2-SHP2 interaction is required for ERK activation in response to IL-2. SRE induction requires both ERK-dependent (via Gab2/SHP2) and Rho-dependent signals. Site-directed mutagenesis (Y614F), co-immunoprecipitation, reporter gene assays (SRE, c-fos), dominant-active/negative RhoA The Biochemical journal High 15170389
2005 Constitutively active STAT5 (caSTAT5) induces persistent tyrosine phosphorylation of GAB2 and formation of a complex containing STAT5, GAB2, p85 (PI3K regulatory subunit), and GRB2 (but not SHP2). A Gab2-3YF mutant incapable of binding PI3K inhibits caSTAT5-induced proliferation and survival, as well as ERK1/2 and Akt phosphorylation, demonstrating GAB2 is required for caSTAT5-mediated activation of both PI3K/Akt and Ras/MAPK pathways. Co-immunoprecipitation, GAB2 mutant (3YF) expression, proliferation/survival assays, signaling analysis The Biochemical journal High 15833084
2005 GAB2 overexpression in breast cancer promotes mammary cell proliferation in 3D culture; these effects require GAB2 binding to GRB2 and SHP2, and are enhanced by PI3K recruitment. GAB2 overexpression mediates hyperactivation of the SHP2-ERK pathway, and co-expression with Neu results in an invasive phenotype. Gab2 potentiates, and Gab2 deficiency ameliorates, Neu-evoked breast carcinogenesis in mice. 3D Matrigel culture, Gab2 knockout mice with Neu transgene, GAB2 domain mutants (Grb2 and Shp2 binding), signaling analysis Nature medicine High 16369543
2005 GAB2 associates with RANK and mediates RANK-induced activation of NF-κB, Akt, and JNK. Gab2-deficient mice develop osteopetrosis with decreased bone resorption due to defective osteoclast differentiation, establishing GAB2 as essential for RANK signaling and osteoclastogenesis. Gab2 knockout mice, osteoclastogenesis assays, co-immunoprecipitation (GAB2-RANK), signaling analysis (NF-κB, Akt, JNK), bone histomorphometry Nature medicine High 15750601
2006 PLCγ2 forms a complex with GAB2 in osteoclasts, is required for GAB2 phosphorylation, and modulates GAB2 recruitment to RANK during RANKL-induced osteoclastogenesis. PLCgamma2 and GAB2 interact downstream of Dap12/FcRγ receptors to regulate NFATc1 activation. Co-immunoprecipitation (PLCγ2-GAB2 complex), PLCγ2 knockout mice, PLCγ inhibitor U73122, RANKL stimulation assays The Journal of clinical investigation High 17053833
2006 GAB2 mediates Kit-evoked mast cell proliferation via the Rac/JNK pathway through SHP2. Kit Tyr567 (an SFK binding site) and SFK activity are required for GAB2 tyrosyl phosphorylation and GAB2-SHP2 association. GAB2 via SHP2 activates Rac/JNK and Ras to control mast cell proliferation, acting in a parallel pathway to PI3K from Kit Tyr719. Gab2 knockout mast cells, re-expression of wild-type GAB2 and SHP2-binding defective mutant, compound Gab2-/- KitY719F/Y719F mice, signaling assays (Rac, JNK, Ras), SFK inhibitors The Journal of biological chemistry High 16873377
2007 GAB2 ablation severely suppresses lung metastasis of Neu-induced mammary tumors. Gab2-deficient cancer cells exhibit decreased migration and impaired ERK activation; defects are rescued by re-introduction of Gab2, establishing GAB2 as a promoter of mammary tumor metastasis via the ERK pathway. Gab2 knockout mice crossed with Neu transgenic mice, lung metastasis assays, cell migration assays, ERK signaling, Gab2 re-expression Oncogene High 17310989
2007 GAB2 was detected in neurons, tangle-bearing neurons, and dystrophic neurites in Alzheimer's disease brain; interference with GAB2 gene expression increased tau phosphorylation, suggesting GAB2 influences Alzheimer's neuropathology. Immunohistochemistry, siRNA-mediated GAB2 knockdown with tau phosphorylation readout Neuron Medium 17553421
2008 Growth factor-induced phosphorylation of GAB2 on S210 and T391 recruits 14-3-3 proteins, which terminates GAB2 signaling by promoting dissociation of GAB2 from GRB2 and receptor complexes. GAB2-S210A/T391A double mutant exhibits sustained receptor association and signaling and promotes cell proliferation and transformation; introduction of constitutive 14-3-3 binding sites renders GAB2 refractory to receptor activation. Site-directed mutagenesis, co-immunoprecipitation, proliferation/transformation assays, constitutive 14-3-3-binding site insertions The EMBO journal High 19172738
2008 In imatinib-resistant CML cells, Lyn kinase complexes with GAB2 and c-Cbl in a BCR-ABL-independent manner and mediates persistent tyrosine phosphorylation of GAB2 and BCR-ABL. Lyn silencing or inhibition is required to suppress GAB2 phosphorylation and restore imatinib sensitivity. Co-immunoprecipitation (Lyn-Gab2 complex), Lyn siRNA, kinase inhibitors, phosphorylation assays in imatinib-resistant patient samples Blood Medium 18235045
2008 GAB2 is involved in differential PI3K/Akt signaling between two splice forms of c-Kit (GNNK- and GNNK+). GNNK- c-Kit mediates stronger PI3K/Akt activation through association with GAB2 and Src-mediated phosphorylation of GAB2, independent of direct PI3K binding to c-Kit. siRNA knockdown of GAB2 confirmed its role in PI3K/Akt activation downstream of c-Kit. siRNA, co-immunoprecipitation, signaling assays, c-Kit splice variant expression in Ba/F3 cells The Journal of biological chemistry Medium 18697750
2009 Crystal structures of two GAB2 epitopes (Gab2a and Gab2b) complexed with the Grb2 SH3C domain reveal distinct binding modes: Gab2b contains a 3(10) helix positioning Arg and Lys of the RxxK motif in parallel orientation, while Gab2a has the RxxK motif in a PPII helix with staggered orientation. Two GRB2 SH3C binding sites in GAB2 are required for the GAB2-GRB2 interaction. Crystal structures, peptide arrays, isothermal titration calorimetry Structure High 19523899
2009 GAB2 overexpression promotes migration and invasion of melanoma cells; Gab2 knockdown reduces these behaviors. GAB2 mediates hyperactivation of Akt signaling in the absence of growth factors. PI3K/Akt pathway inhibition decreases Gab2-mediated tumor cell migration and invasive potential. GAB2 overexpression results in enhanced tumor growth and metastatic potential in vivo. Gab2 siRNA, overexpression, PI3K inhibitor treatment, migration/invasion assays, in vivo xenograft model The American journal of pathology Medium 19342374
2010 GAB2 overexpression in mammary epithelial cells decreases RhoA activation, reduces stress fibers and focal adhesions, and enhances cell migration via Shp2-dependent signaling. GAB2 promotes Vav2 phosphorylation and plasma membrane recruitment of p190A RhoGAP, which negatively regulates RhoA; constitutively active RhoA restores stress fibers in GAB2-expressing cells. A Gab2 mutant lacking Shp2 binding sites does not affect RhoA or cellular phenotype. Overexpression and Gab2 mutants (ΔShp2, 2xA), RhoA activity assays, p190A RhoGAP knockdown, co-immunoprecipitation, constitutively active RhoA rescue Molecular biology of the cell High 21118992
2011 GAB2 via PI3K/ARF1 signaling regulates mast cell degranulation. Using Gab2 knock-in mice with mutations at either the PI3K or SHP2 binding sites, both binding sites are required for degranulation and anaphylaxis (but not cytokine production). The PI3K binding site of GAB2 is specifically required for granule translocation; FcεRI-stimulated ARF1 activation is dependent on Fyn and the PI3K binding site of GAB2. Gab2 knock-in mice (PI3K- and SHP2-binding site mutations), degranulation assays, ARF1 activation assay, anaphylaxis models, granule imaging Journal of immunology High 21653832
2011 GAB2 overexpression in ovarian cancer cells promotes migration and invasion and downregulates E-cadherin expression via PI3K pathway activation, leading to upregulation of ZEB1 (an EMT transcription factor). PI3K inhibitors reverse Gab2-induced EMT effects. GAB2 mutants defective in PI3K activation (not SHP2-ERK) abolish these effects, specifying the PI3K pathway as responsible. Overexpression, knockdown, GAB2 domain mutants (PI3K and Shp2-Erk defective), PI3K inhibitors, E-cadherin and Zeb1 expression assays, migration/invasion assays Oncogene High 21996746
2011 GAB2 mediates G-CSF receptor activation of the Src kinase Lyn by recruiting SHP2. After G-CSF stimulation, Lyn associates with GAB2; GAB2-recruited SHP2 dephosphorylates inhibitory pLyn-Tyr507, enabling Lyn activation. This mechanism requires the Gab2-SHP2 interaction, as a mutant Gab2 unable to bind SHP2 fails to support Tyr507 dephosphorylation. Co-immunoprecipitation, Gab2 siRNA, SHP2-deficient cells, in vitro phosphatase assay with constitutively active Shp2E76A, Lyn Tyr507/Tyr396 phosphorylation analysis, GAB2 mutants Blood High 21636860
2012 GAB2 is an A-kinase anchoring protein (AKAP) that binds the type I regulatory subunit of PKA; PKA phosphorylates GAB2 on Ser159. GAB2 is present in a preformed complex with PI3K and IRS-1 in granulosa cells. Overexpression of GAB2 enhances FSH-stimulated AKT phosphorylation, establishing GAB2 as a coordinator of PKA-to-PI3K/AKT signaling in FSH-stimulated ovarian granulosa cells. Co-immunoprecipitation, PKA in vitro phosphorylation assay, GAB2 overexpression, AKT phosphorylation assays in granulosa cells Proceedings of the National Academy of Sciences of the United States of America High 23045700
2013 RSK (p90 ribosomal S6 kinase) phosphorylates GAB2 on three conserved residues (in vitro and in vivo), downstream of Ras/MAPK pathway activation. RSK-mediated phosphorylation of GAB2 inhibits SHP2 recruitment without affecting GRB2 binding. An unphosphorylatable GAB2 mutant promotes invasion-like phenotype and increased cell motility, placing RSK in a negative-feedback loop restricting GAB2-dependent epithelial cell motility. In vitro RSK kinase assay, mass spectrometry phosphorylation sites, site-directed mutagenesis, co-immunoprecipitation, cell migration/invasion assays Molecular and cellular biology High 23401857
2015 Crystal structure of ISIR-005 in complex with 14-3-3 and the GAB2 binding motif (Gab2pS210pT391) shows that the small molecule stabilizes the 14-3-3/GAB2 interaction at the pT391 site by occupying a pre-formed pocket at the rim of the interface. The Gab2pS210 motif binding does not create an interface pocket suitable for the molecule. Crystal structure of ternary complex, isothermal titration calorimetry, biochemical stabilization assay ChemMedChem High 26644359
2016 GAB2 deficiency in Ptpn11E76K/+ (leukemic Shp2 gain-of-function) mice markedly attenuates myeloproliferative neoplasia, including reduced myeloid overproduction, splenomegaly, and myeloid infiltration. The interaction between leukemia-associated mutant SHP2 and GAB2 is enhanced, and the mTOR pathway is elevated in leukemic cells. Rapamycin treatment of Ptpn11E76K/+ mice mitigates MPN phenotypes, placing GAB2-PI3K-mTOR downstream of mutant SHP2. Double mutant mice (Ptpn11E76K/+/Gab2-/-), myeloid differentiation assays, Rapamycin treatment, signaling analysis Leukemia High 27840422
2016 GAB2 is essential for both myeloid and lymphoid leukemogenesis by BCR-ABL1. Gab2 knockout mice transplanted with BCR-ABL1-transduced bone marrow fail to develop CML-like disease; this is restored by wild-type GAB2 but not by GAB2 mutants lacking PI3K or SHP2 binding sites. Both PI3K and SHP2 binding sites are required for myeloid (CML) transformation, while only the SHP2 binding site is required for lymphoid (B-ALL) leukemogenesis. Mouse models of CML and B-ALL with Gab2 KO, GAB2 domain mutant rescue, signaling analysis Blood High 26773044
2017 In zebrafish MYCN-transgenic neuroblastoma model, GAB2 overexpression activates the SHP2-Ras-ERK pathway, promotes proliferation of hyperplastic neuroblasts, and increases neuroblastoma tumor penetrance, cooperating with MYCN. This establishes GAB2 as a SHP2 activator that cooperates with MYCN in neuroblastomagenesis. Zebrafish MYCN transgenic model, GAB2 overexpression, ptpn11 gain-of-function mutants, ERK signaling analysis Cell reports Medium 28329685
2017 YAP and TAZ transcriptional regulators maintain PI3K pathway activation in endometrial cancer cells by transcriptionally regulating GAB2 levels. Coordinate knockdown of YAP and TAZ markedly decreases constitutive and growth factor-induced PI3K pathway activation by reducing GAB2 protein levels. siRNA knockdown of YAP/TAZ, GAB2 protein level measurement, PI3K/AKT signaling assays, in vivo tumor growth Cancer research Medium 28202507
2017 In IL-4/M2 macrophage polarization, GAB2 is recruited to the IL-4 receptor and synergistically enhances downstream signaling; loss of GAB2 suppresses STAT6 activation in response to IL-4, while loss of GAB1 attenuates AKT activation. GAB2 and GAB1 have non-redundant roles in M2 macrophage polarization and bleomycin-induced pulmonary fibrosis. Gab2 knockout mice, Gab1 conditional KO mice (macrophage-specific), IL-4 signaling assays, M2 polarization markers, bleomycin-induced fibrosis model, co-immunoprecipitation The Journal of biological chemistry High 28687632
2019 Loss of PIK3R1 (p85α) in ovarian cancer cells alters GAB2 phosphorylation, relieves negative inhibition on AKT, and promotes assembly of a JAK2/STAT3 signalosome through GAB2 phosphorylation changes. This establishes GAB2 as a node linking PIK3R1 loss to both AKT and JAK2/STAT3 pathway activation. PIK3R1 siRNA knockdown, GAB2 phosphorylation analysis, AKT and STAT3 signaling assays, co-immunoprecipitation Nature communications Medium 30755611
2022 GAB2 facilitates assembly of the CBM (CARMA3-BCL10-MALT1) signalosome in endothelial cells, which mediates Rho and NF-κB activation in response to IL-1β. GAB2 silencing reduces IL-1β-induced Rho-dependent exocytosis of P-selectin and VWF, NF-κB-dependent tissue factor expression, neutrophil adhesion, and venous thrombosis in mice. Gab2 gene silencing, MALT1 pharmacological inhibition (mepazine), inferior vena cava ligation model, P-selectin and VWF exocytosis assays, NF-κB signaling analysis Blood High 35895897
2009 A unique domain in RANK (HCR, highly conserved region) recruits GAB2, which further associates with PLCγ2 in late-phase RANK signaling. HCR is dispensable for early RANK/ITAM signaling but essential for sustained NF-κB and PLCγ2/NFATc1 activation required for osteoclastogenesis. Co-immunoprecipitation (GAB2-HCR, GAB2-PLCγ2), RANK domain deletion/mutation analysis, NFATc1 reporter assays, osteoclast differentiation assays Genes to cells Medium 19845770
2008 G-CSF stimulates Jak2-dependent phosphorylation of Gab2 on Tyr643, which promotes Shp2 binding to GAB2 and Erk1/2 activation and cell proliferation. In vitro, activated Jak2 directly phosphorylates GAB2 tyrosine residues; mutation of Y643 inhibits G-CSF-stimulated Erk1/2 activation, Shp2 binding, and Gab2-mediated cell proliferation. In vitro Jak2 kinase assay on GAB2, Jak2 antisense/dominant-negative constructs, Y643F mutagenesis, co-immunoprecipitation, Erk1/2 activation, cell proliferation assays Cellular signalling High 18644434

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 GAB2 alleles modify Alzheimer's risk in APOE epsilon4 carriers. Neuron 371 17553421
2002 Critical role for Gab2 in transformation by BCR/ABL. Cancer cell 276 12124177
1998 Cloning of p97/Gab2, the major SHP2-binding protein in hematopoietic cells, reveals a novel pathway for cytokine-induced gene activation. Molecular cell 271 9885561
2001 Essential role for Gab2 in the allergic response. Nature 255 11449275
2006 PLCgamma2 regulates osteoclastogenesis via its interaction with ITAM proteins and GAB2. The Journal of clinical investigation 170 17053833
2005 A role for the scaffolding adapter GAB2 in breast cancer. Nature medicine 170 16369543
2005 The molecular scaffold Gab2 is a crucial component of RANK signaling and osteoclastogenesis. Nature medicine 138 15750601
2012 PKA and GAB2 play central roles in the FSH signaling pathway to PI3K and AKT in ovarian granulosa cells. Proceedings of the National Academy of Sciences of the United States of America 122 23045700
1999 Gab2, a new pleckstrin homology domain-containing adapter protein, acts to uncouple signaling from ERK kinase to Elk-1. The Journal of biological chemistry 114 10391903
2002 Requirement of Gab2 for mast cell development and KitL/c-Kit signaling. Blood 113 11861309
2005 Increased proliferation and altered growth factor dependence of human mammary epithelial cells overexpressing the Gab2 docking protein. The Journal of biological chemistry 98 16253990
2005 Activated STAT5 proteins induce activation of the PI 3-kinase/Akt and Ras/MAPK pathways via the Gab2 scaffolding adapter. The Biochemical journal 91 15833084
2008 Lyn regulates BCR-ABL and Gab2 tyrosine phosphorylation and c-Cbl protein stability in imatinib-resistant chronic myelogenous leukemia cells. Blood 90 18235045
2005 Enhanced sensitivity to inhibition of SHP2, STAT5, and Gab2 expression in chronic myeloid leukemia (CML). Blood 90 16278304
2003 Critical role for scaffolding adapter Gab2 in Fc gamma R-mediated phagocytosis. The Journal of cell biology 89 12821647
2000 Flt3 ligand induces tyrosine phosphorylation of gab1 and gab2 and their association with shp-2, grb2, and PI3 kinase. Biochemical and biophysical research communications 89 11027663
2012 GAB2--a scaffolding protein in cancer. Molecular cancer research : MCR 84 22871571
1999 Engagement of Gab1 and Gab2 in erythropoietin signaling. The Journal of biological chemistry 84 10455108
2002 The docking protein Gab2 is overexpressed and estrogen regulated in human breast cancer. Oncogene 78 12140767
2007 Role of Gab2 in mammary tumorigenesis and metastasis. Oncogene 75 17310989
2001 Scaffolding protein Gab2 mediates differentiation signaling downstream of Fms receptor tyrosine kinase. Molecular and cellular biology 74 11287610
2000 The docking molecule gab2 is induced by lymphocyte activation and is involved in signaling by interleukin-2 and interleukin-15 but not other common gamma chain-using cytokines. The Journal of biological chemistry 71 10849428
2002 PKB-mediated negative feedback tightly regulates mitogenic signalling via Gab2. The EMBO journal 70 11782427
2009 Gab2-mediated signaling promotes melanoma metastasis. The American journal of pathology 68 19342374
2009 Distinct binding modes of two epitopes in Gab2 that interact with the SH3C domain of Grb2. Structure (London, England : 1993) 68 19523899
2006 The scaffolding adapter Gab2, via Shp-2, regulates kit-evoked mast cell proliferation by activating the Rac/JNK pathway. The Journal of biological chemistry 67 16873377
2001 Docking protein Gab2 is phosphorylated by ZAP-70 and negatively regulates T cell receptor signaling by recruitment of inhibitory molecules. The Journal of biological chemistry 67 11572860
2011 Gab2 regulates the migratory behaviors and E-cadherin expression via activation of the PI3K pathway in ovarian cancer cells. Oncogene 66 21996746
2005 Participation of both Gab1 and Gab2 in the activation of the ERK/MAPK pathway by epidermal growth factor. The Biochemical journal 64 15952937
2016 Gab2 facilitates epithelial-to-mesenchymal transition via the MEK/ERK/MMP signaling in colorectal cancer. Journal of experimental & clinical cancer research : CR 61 26754532
2009 Focal amplification and oncogene dependency of GAB2 in breast cancer. Oncogene 60 19881546
2015 Structure and function of Gab2 and its role in cancer (Review). Molecular medicine reports 59 26095858
2004 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. The Journal of biological chemistry 59 15010462
2002 Regulation of the Erk2-Elk1 signaling pathway and megakaryocytic differentiation of Bcr-Abl(+) K562 leukemic cells by Gab2. Blood 59 11830491
2015 Small-Molecule Stabilization of the 14-3-3/Gab2 Protein-Protein Interaction (PPI) Interface. ChemMedChem 55 26644359
2015 Overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating chemokine expression. Oncogene 55 26657155
2000 Cutting edge: gab2 mediates an inhibitory phosphatidylinositol 3'-kinase pathway in T cell antigen receptor signaling. Journal of immunology (Baltimore, Md. : 1950) 54 11035047
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
2008 Phosphorylation-dependent binding of 14-3-3 terminates signalling by the Gab2 docking protein. The EMBO journal 50 19172738
2002 Distinct recruitment and function of Gab1 and Gab2 in Met receptor-mediated epithelial morphogenesis. Molecular biology of the cell 50 12058075
2009 GAB2 amplifications refine molecular classification of melanoma. Clinical cancer research : an official journal of the American Association for Cancer Research 49 19509136
2012 Gab2 signaling in chronic myeloid leukemia cells confers resistance to multiple Bcr-Abl inhibitors. Leukemia 48 22858987
2008 Gab2 is involved in differential phosphoinositide 3-kinase signaling by two splice forms of c-Kit. The Journal of biological chemistry 48 18697750
2017 YAP/TAZ-Mediated Upregulation of GAB2 Leads to Increased Sensitivity to Growth Factor-Induced Activation of the PI3K Pathway. Cancer research 47 28202507
2016 Inhibition of the Gab2/PI3K/mTOR signaling ameliorates myeloid malignancy caused by Ptpn11 (Shp2) gain-of-function mutations. Leukemia 47 27840422
2003 Gads/Grb2-mediated association with LAT is critical for the inhibitory function of Gab2 in T cells. Molecular and cellular biology 46 12640133
2003 G-CSF-induced tyrosine phosphorylation of Gab2 is Lyn kinase dependent and associated with enhanced Akt and differentiative, not proliferative, responses. Blood 46 14656892
2006 GAB2 is a novel target of 11q amplification in AML/MDS. Genes, chromosomes & cancer 44 16736498
2002 Role of the docking protein Gab2 in beta(1)-integrin signaling pathway-mediated hematopoietic cell adhesion and migration. Blood 44 11895767
2022 Targeting SNORA38B attenuates tumorigenesis and sensitizes immune checkpoint blockade in non-small cell lung cancer by remodeling the tumor microenvironment via regulation of GAB2/AKT/mTOR signaling pathway. Journal for immunotherapy of cancer 42 35577506
2003 GC-GAP, a Rho family GTPase-activating protein that interacts with signaling adapters Gab1 and Gab2. The Journal of biological chemistry 42 12819203
2001 A yeast two-hybrid study of human p97/Gab2 interactions with its SH2 domain-containing binding partners. FEBS letters 42 11334882
2007 Abnormal hematopoiesis in Gab2 mutant mice. Blood 41 17374739
2005 A novel role for Gab2 in bFGF-mediated cell survival during retinoic acid-induced neuronal differentiation. The Journal of cell biology 40 16009726
2001 Phosphoinositide 3-kinase-dependent regulation of interleukin-3-induced proliferation: involvement of mitogen-activated protein kinases, SHP2 and Gab2. The Journal of biological chemistry 40 11335710
2019 Deregulated Gab2 phosphorylation mediates aberrant AKT and STAT3 signaling upon PIK3R1 loss in ovarian cancer. Nature communications 39 30755611
2018 BRAF inhibition upregulates a variety of receptor tyrosine kinases and their downstream effector Gab2 in colorectal cancer cell lines. Oncogene 38 29326440
2007 Gab2 and Src co-operate in human mammary epithelial cells to promote growth factor independence and disruption of acinar morphogenesis. Oncogene 38 17998934
2014 In vivo multiplexed interrogation of amplified genes identifies GAB2 as an ovarian cancer oncogene. Proceedings of the National Academy of Sciences of the United States of America 37 24385586
2007 Increased expression of Gab2, a scaffolding adaptor of the tyrosine kinase signalling, in gastric carcinomas. Pathology 37 17558859
2022 The Gab2-MALT1 axis regulates thromboinflammation and deep vein thrombosis. Blood 36 35895897
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
2002 The adapter molecule Gab2 regulates Fc epsilon RI-mediated signal transduction in mast cells. Journal of immunology (Baltimore, Md. : 1950) 36 11971018
2017 Elevated Gab2 induces tumor growth and angiogenesis in colorectal cancer through upregulating VEGF levels. Journal of experimental & clinical cancer research : CR 35 28420432
2015 Meta-analysis of the Association between Alzheimer Disease and Variants in GAB2, PICALM, and SORL1. Molecular neurobiology 34 26611835
2011 Gab2, via PI-3K, regulates ARF1 in FcεRI-mediated granule translocation and mast cell degranulation. Journal of immunology (Baltimore, Md. : 1950) 34 21653832
2010 The limited contribution of Fyn and Gab2 to the high affinity IgE receptor signaling in mast cells. The Journal of biological chemistry 33 20335178
2002 Epidermal growth factor-induced DNA synthesis. Key role for Src phosphorylation of the docking protein Gab2. The Journal of biological chemistry 33 12464621
2009 GAB2 as an Alzheimer disease susceptibility gene: follow-up of genomewide association results. Archives of neurology 32 19204163
2011 G-CSF receptor activation of the Src kinase Lyn is mediated by Gab2 recruitment of the Shp2 phosphatase. Blood 31 21636860
2008 Association study of the GAB2 gene with the risk of developing Alzheimer's disease. Neurobiology of disease 31 18272374
2004 Interaction of the tyrosine phosphatase SHP-2 with Gab2 regulates Rho-dependent activation of the c-fos serum response element by interleukin-2. The Biochemical journal 31 15170389
2012 Gab2 expression in glioma and its implications for tumor invasion. Acta oncologica (Stockholm, Sweden) 30 23231021
2008 The GAB2 gene and the risk of Alzheimer's disease: replication and meta-analysis. Biological psychiatry 30 19118819
2000 Recruitment of the protein-tyrosine phosphatase SHP-2 to the C-terminal tyrosine of the prolactin receptor and to the adaptor protein Gab2. The Journal of biological chemistry 30 10991949
2017 Variants in BAK1, SPRY4, and GAB2 are associated with pediatric germ cell tumors: A report from the children's oncology group. Genes, chromosomes & cancer 28 28295819
2017 Critical Role for GAB2 in Neuroblastoma Pathogenesis through the Promotion of SHP2/MYCN Cooperation. Cell reports 28 28329685
2013 Gab2 phosphorylation by RSK inhibits Shp2 recruitment and cell motility. Molecular and cellular biology 28 23401857
2007 A novel Stat3 binding motif in Gab2 mediates transformation of primary hematopoietic cells by the Stk/Ron receptor tyrosine kinase in response to Friend virus infection. Molecular and cellular biology 28 17353274
2019 Gab2 promotes cancer stem cell like properties and metastatic growth of ovarian cancer via downregulation of miR-200c. Experimental cell research 27 31194976
2009 A unique domain in RANK is required for Gab2 and PLCgamma2 binding to establish osteoclastogenic signals. Genes to cells : devoted to molecular & cellular mechanisms 27 19845770
2018 miR-486-5p inhibits cell proliferation and invasion through repressing GAB2 in non-small cell lung cancer. Oncology letters 26 30127957
2012 GAB2 induces tumor angiogenesis in NRAS-driven melanoma. Oncogene 26 22926523
2009 A role of Gab2 association in Flt3 ITD mediated Stat5 phosphorylation and cell survival. British journal of haematology 26 19438505
2017 Gab2 mediates hepatocellular carcinogenesis by integrating multiple signaling pathways. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 25 28842424
2010 Overexpression of the oncogenic signal transducer Gab2 occurs early in breast cancer development. International journal of cancer 25 20087860
2009 Common variation in GRB-associated Binding Protein 2 (GAB2) and increased risk for Alzheimer dementia. Human mutation 25 18853460
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
2015 Enhanced GAB2 Expression Is Associated with Improved Survival in High-Grade Serous Ovarian Cancer and Sensitivity to PI3K Inhibition. Molecular cancer therapeutics 24 25852062
2012 Participation of Gab1 and Gab2 in IL-22-mediated keratinocyte proliferation, migration, and differentiation. Molecular and cellular biochemistry 24 22851227
2010 The Gab2 in signal transduction and its potential role in the pathogenesis of Alzheimer's disease. Neuroscience bulletin 24 20502503
2009 GAB2 gene does not modify the risk of Alzheimer's disease in Spanish APOE 4 carriers. The journal of nutrition, health & aging 23 19262956
2020 The miR-218/GAB2 axis regulates proliferation, invasion and EMT via the PI3K/AKT/GSK-3β pathway in prostate cancer. Experimental cell research 22 32522441
2017 microRNA-302c-3p inhibits renal cell carcinoma cell proliferation by targeting Grb2-associated binding 2 (Gab2). Oncotarget 22 28412750
2016 GAB2 promotes cell proliferation by activating the ERK signaling pathway in hepatocellular carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 22 27026230
2008 G-CSF stimulates Jak2-dependent Gab2 phosphorylation leading to Erk1/2 activation and cell proliferation. Cellular signalling 22 18644434
2008 GAB2 is not associated with late-onset Alzheimer's disease in Japanese. European journal of human genetics : EJHG 22 18854865
2016 Distinct GAB2 signaling pathways are essential for myeloid and lymphoid transformation and leukemogenesis by BCR-ABL1. Blood 21 26773044
2016 Deletion of Gab2 in mice protects against hepatic steatosis and steatohepatitis: a novel therapeutic target for fatty liver disease. Journal of molecular cell biology 21 27282405
2010 Gab2 regulates cytoskeletal organization and migration of mammary epithelial cells by modulating RhoA activation. Molecular biology of the cell 21 21118992