Affinage

GRB10

Growth factor receptor-bound protein 10 · UniProt Q13322

Length
594 aa
Mass
67.2 kDa
Annotated
2026-04-28
100 papers in source corpus 50 papers cited in narrative 50 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRB10 is a multi-domain adaptor protein that functions as a central negative regulator of receptor tyrosine kinase signaling, particularly insulin receptor (IR) and IGF-1 receptor (IGF-1R), integrating growth factor inputs with nutrient-sensing pathways to control growth, metabolism, and cell survival. Its BPS domain acts as a pseudosubstrate inhibitor of IR/IGF-1R kinase activity (PMID:11287005), while its SH2 domain physically blocks IRS protein access to activated receptors, thereby attenuating PI3K/Akt and MAPK signaling (PMID:12493740, PMID:14615605); simultaneously, GRB10 recruits the E3 ubiquitin ligase NEDD4 to promote receptor multiubiquitination, internalization, and degradation (PMID:12697834, PMID:18286479). mTORC1 phosphorylates GRB10 to stabilize it, creating a feedback loop that restrains PI3K and MAPK pathways; in adipose tissue, this phosphorylation switches GRB10 binding from IR to raptor, thereby downregulating mTORC1 itself (PMID:21659605, PMID:24746805). In vivo, maternal-allele GRB10 loss causes fetal overgrowth and enhanced insulin sensitivity, while paternal-allele loss in brain increases social dominance behavior, and in hypothalamic neurons GRB10 enhances leptin receptor signaling to regulate energy homeostasis (PMID:12829789, PMID:21270893, PMID:36593271).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1995 Medium

    Identification of GRB10 as a new SH2-containing adaptor protein that binds activated receptor tyrosine kinases established it as a candidate signaling intermediate downstream of growth factor receptors.

    Evidence Expression library screening with phosphorylated EGF receptor; yeast two-hybrid and GST pulldowns with RET receptor

    PMID:7665556 PMID:7731717

    Open questions at the time
    • No functional consequence of GRB10–RTK interaction determined
    • Signaling role (positive vs. negative) unknown
  2. 1996 High

    Mapping GRB10 SH2 domain binding to specific phosphotyrosines on the insulin receptor and IGF-1R defined the molecular basis of its receptor specificity and raised the question of whether GRB10 promotes or inhibits insulin/IGF signaling.

    Evidence Yeast two-hybrid, GST pulldowns, phosphopeptide binding (IR pY1322), microinjection of SH2 domain fusion proteins; multiple independent labs

    PMID:8621530 PMID:8764099 PMID:8798417

    Open questions at the time
    • Positive vs. negative signaling role debated
    • BPS domain not yet discovered
    • In vivo relevance unknown
  3. 1998 High

    Discovery of the BPS domain as a second receptor-binding module that cooperates with the SH2 domain revealed a bipartite receptor engagement mechanism unique to the Grb7/10/14 family.

    Evidence Domain deletion/mutagenesis with GST pulldown and yeast two-hybrid using mutant IR/IGF-1R (activation loop tyrosine mutants)

    PMID:9506989

    Open questions at the time
    • BPS domain mechanism of action (pseudosubstrate inhibition) not yet demonstrated
    • Structural basis undefined
  4. 2001 High

    Demonstration that the BPS domain directly inhibits IR/IGF-1R kinase activity toward substrates in a reconstituted system established GRB10 as a bona fide kinase inhibitor, not merely a docking partner.

    Evidence In vitro kinase assay with purified recombinant BPS domain and IR/IGF-1R kinase domains, peptide competition

    PMID:11287005

    Open questions at the time
    • In vivo relevance of BPS-mediated inhibition not yet shown
    • Relative contribution of BPS vs. SH2 in intact cells unclear
  5. 2002 High

    Resolving the positive-vs-negative debate: GRB10 SH2 domain physically blocks IRS-1/IRS-2 access to the insulin receptor, attenuating PI3K/Akt signaling, while RNAi depletion enhances insulin signaling—establishing GRB10 as a negative regulator.

    Evidence Stable overexpression and RNAi knockdown in CHO/IR cells and adipocytes, yeast tri-hybrid showing competitive exclusion of IRS

    PMID:12493740

    Open questions at the time
    • In vivo confirmation in whole animals pending
    • Contribution to MAPK pathway inhibition not yet addressed
  6. 2003 High

    GRB10 was shown to recruit the E3 ligase NEDD4 to IGF-1R, promoting receptor ubiquitination, internalization, and degradation—revealing a second inhibitory mechanism beyond kinase/substrate blockade.

    Evidence Triple-complex co-IP (GRB10–NEDD4–IGF-1R), catalytically inactive NEDD4 mutant, pulse-chase receptor half-life, proteasome/lysosome inhibitors

    PMID:12697834

    Open questions at the time
    • Ubiquitin chain topology on IGF-1R not characterized
    • Whether NEDD4 recruitment also targets IR in vivo uncertain
  7. 2003 High

    Crystal structures of the SH2 domain (homodimer at 1.65 Å) revealed how the Grb7/10/14 family recognizes dimeric phosphotyrosine motifs on the IR/IGF-1R activation loop, providing the first structural framework for GRB10-receptor interaction.

    Evidence X-ray crystallography, analytical ultracentrifugation

    PMID:12551896

    Open questions at the time
    • Full-length GRB10 structure unavailable
    • BPS domain structure not yet solved for GRB10
  8. 2003 High

    Maternal-allele Grb10 knockout mice exhibited ~30% embryonic overgrowth, genetically establishing GRB10 as a maternally imprinted growth suppressor acting on a pathway distinct from IGF-2.

    Evidence Gene-trap knockout crossed with Igf2 mutant mice (epistasis analysis), body/placenta weight measurements

    PMID:12829789

    Open questions at the time
    • Tissue-specific contributions to overgrowth not dissected
    • Receptor target in placenta not defined
  9. 2007 High

    Whole-body insulin sensitivity measurements in Grb10-deficient mice using hyperinsulinemic-euglycemic clamps confirmed that GRB10 constrains insulin signaling in vivo, with enhanced Akt and MAPK phosphorylation in muscle and fat.

    Evidence Gene-trap knockout mice, hyperinsulinemic-euglycemic clamp, tissue-level signaling immunoblots

    PMID:17562854 PMID:17620412

    Open questions at the time
    • Cell-autonomous vs. systemic effects not separated
    • Brain-specific functions of paternal allele not yet known
  10. 2010 High

    The crystal structure of the NEDD4 C2–GRB10 SH2 complex showed that NEDD4 binds GRB10 at sites distinct from the phosphotyrosine pocket, explaining how GRB10 can simultaneously engage both NEDD4 and the receptor kinase domain to bridge them.

    Evidence X-ray crystallography at 2.0 Å resolution, structural interface analysis

    PMID:20980250

    Open questions at the time
    • No full ternary complex structure (GRB10–NEDD4–receptor)
    • Stoichiometry and dynamics in vivo not resolved
  11. 2011 High

    Identification of GRB10 as a direct mTORC1 substrate whose phosphorylation-dependent stabilization mediates feedback inhibition of both PI3K and MAPK pathways placed GRB10 at a critical node linking nutrient sensing to growth factor signaling.

    Evidence Large-scale quantitative phosphoproteomics, rapamycin treatment, loss-of-function experiments

    PMID:21659605

    Open questions at the time
    • Specific phosphorylation sites in human GRB10 partially mapped
    • Phosphatase(s) that dephosphorylate GRB10 unknown
  12. 2011 High

    Demonstration that the paternal Grb10 allele is selectively expressed in brain and controls social dominance behavior revealed an unexpected imprinting-based functional partition: maternal allele governs peripheral growth, paternal allele governs behavior.

    Evidence Allele-specific knockout mice, behavioral testing panels (social dominance, allogrooming)

    PMID:21270893

    Open questions at the time
    • Molecular mechanism of GRB10 in social behavior unknown
    • Receptor partners in brain neurons not identified at this time
  13. 2014 High

    Discovery that mTOR-mediated phosphorylation switches GRB10 binding from insulin receptor to raptor, causing mTORC1 dissociation and downregulation in adipose tissue, revealed a phosphorylation-dependent partner-switching mechanism integrating GRB10 into bidirectional mTORC1 feedback.

    Evidence Phospho-site mutant analysis, co-IP of GRB10–raptor complex, fat-specific Grb10 KO mice, rapamycin rescue in vivo

    PMID:24746805

    Open questions at the time
    • Whether raptor-switching occurs in all tissues or is fat-specific
    • Structural basis of phospho-dependent partner switch unknown
  14. 2018 High

    Muscle-specific GRB10 deletion confirmed cell-autonomous control of insulin-stimulated glucose uptake and fiber size, establishing that the metabolic and growth phenotypes of global knockouts originate in muscle itself.

    Evidence Muscle-specific conditional knockout (α-skeletal actin-Cre), hyperinsulinemic-euglycemic clamp, insulin signaling immunoblots

    PMID:29370381

    Open questions at the time
    • Developmental vs. postnatal contribution to muscle hypertrophy not fully resolved
    • Whether BPS or SH2 domain is dominant in muscle unclear
  15. 2023 High

    GRB10 was found to interact with the leptin receptor in hypothalamic neurons and enhance leptin signaling, broadening its role from a growth factor signaling inhibitor to a positive modulator of energy homeostasis in the CNS.

    Evidence Neuron-specific conditional KO and AAV-mediated overexpression in AgRP/POMC neurons, patch-clamp electrophysiology, GRB10–leptin receptor co-IP, body weight/food intake measurements

    PMID:36593271

    Open questions at the time
    • Mechanism by which GRB10 enhances (rather than inhibits) leptin receptor signaling not fully defined
    • Whether NEDD4 or BPS domain mechanisms are involved in leptin signaling unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length structural model of GRB10 in complex with activated receptor and NEDD4 is lacking, and the molecular basis for context-dependent switching between positive and negative signaling roles remains unresolved.
  • No full-length GRB10 structure
  • Mechanism determining positive (leptin/VEGFR/c-Kit) vs. negative (IR/IGF-1R) signaling roles unknown
  • Upstream signals controlling allele-specific expression in brain vs. periphery not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 8 GO:0098772 molecular function regulator activity 6
Localization
GO:0005829 cytosol 2 GO:0005739 mitochondrion 1 GO:0005768 endosome 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-392499 Metabolism of proteins 4 R-HSA-1266738 Developmental Biology 3
Partners
GIGYF1GIGYF2IGF1RINSRLEPRNEDD4RAF1RPTOR
Complex memberships
GRB10–NEDD4 complexmTORC1 (via raptor interaction)

Evidence

Reading pass · 50 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 GRB10 was identified as a new SH2 domain-containing adapter protein by screening expression libraries with the phosphorylated EGF receptor C-terminus; it is highly related to Grb7 and undergoes serine (but not tyrosine) phosphorylation after EGF treatment, resulting in a mobility shift. Expression library screen, SH2 domain cloning, phosphorylation assay Oncogene Medium 7731717
1995 GRB10 (SH2 domain) interacts with the RET receptor tyrosine kinase in a kinase-activation-dependent manner, as demonstrated by yeast two-hybrid and GST pulldown assays; this was the first receptor described to use GRB10 as a signaling intermediate. Yeast two-hybrid, GST fusion protein pulldown, in vivo co-immunoprecipitation with EGFR/Ret chimera The Journal of biological chemistry Medium 7665556
1996 GRB10 binds to the insulin receptor and IGF-I receptor via its SH2 domain in a kinase-dependent manner; GRB10 SH2 domain fusion protein microinjection inhibits insulin- and IGF-I-stimulated mitogenesis but not EGF-induced mitogenesis, indicating a positive role in insulin/IGF-I signaling. Yeast two-hybrid, GST pulldown with purified insulin receptor, microinjection of SH2 domain fusion protein The Journal of biological chemistry Medium 8798417
1996 Ligand-activated ELK (Eph-related) receptor recruits GRB10 via its SH2 domain in a phosphorylation-dependent manner; Tyr-929 of ELK was identified as required for GRB10 (but not GRB2) interaction. Yeast two-hybrid, GST-ELKcy pulldown from endothelial cell extracts, site-directed mutagenesis, co-immunoprecipitation after ligand stimulation The Journal of biological chemistry Medium 8798570
1996 GRB10 SH2 domain interacts with the insulin receptor carboxyl terminus (specifically phospho-Tyr-1322) in an insulin-dependent and kinase-dependent manner; GRB10 does not associate with IRS-1, indicating an IRS-1-independent function. Yeast two-hybrid, GST fusion protein pulldown from cell lysates, co-precipitation with purified insulin receptor, phosphopeptide binding The Journal of biological chemistry High 8621530
1996 GRB10 was identified as a direct binding partner of the IGF-I receptor intracellular domain via yeast two-hybrid; binding requires a catalytically active receptor and maps to residues 1229–1245 of the IGF-IR; GRB10 co-precipitates with IGF-IR in cell lysates. Yeast two-hybrid, co-immunoprecipitation, IGF-IR mutant analysis Cancer research Medium 8764099
1996 GRB10 interacts with the IGF-I receptor via its SH2 domain in a kinase-dependent manner; yeast two-hybrid also identified GRB10 as binding to IRS-1 and Shc binding partners of the IGF-IR, and GRB10 interaction does not require the juxtamembrane Tyr-950. Yeast two-hybrid interaction trap, reporter gene activation assay Molecular endocrinology Medium 8776723
1997 GRB10 protein translocates from cytosol to membrane upon insulin stimulation; its SH2 domain binds at least two sites in the insulin receptor (kinase activation loop > juxtamembrane); c-Abl SH3 domain (but not Fyn, PI3K p85, or Grb2 SH3) binds GRB10; GRB10 also binds PDGF and EGF receptors. Cell fractionation/localization, GST pulldown, phosphopeptide binding, co-immunoprecipitation, synthetic mutant receptor analysis The Journal of biological chemistry High 9006901
1997 GRB10 associates preferentially with the insulin receptor compared to the IGF-I receptor in intact mouse fibroblasts; association is hormone-activated and sustained 5–10 min after insulin stimulation. Co-immunoprecipitation from R- cells (IGF-IR knockout) and transfected R-IR or R+ cells The Journal of clinical investigation Medium 9062339
1998 GRB10 contains a second novel receptor-binding domain (BPS domain, ~50 amino acids between the PH and SH2 domains) that interacts with the insulin receptor and IGF-I receptor in a kinase-dependent manner requiring the activation loop tyrosines (Y1150/Y1151); the SH2 and BPS domains cooperate to determine receptor binding specificity. Domain deletion/mutagenesis analysis, GST pulldown, yeast two-hybrid with mutant receptors The Journal of biological chemistry High 9506989
1998 GRB10 SH2 domain interacts in a phosphotyrosine-independent manner with Raf-1 and MEK1 kinases; interaction with MEK1 requires insulin treatment and follows MAP kinase activation; overexpression of GRB10 SH2 domain mutants promotes apoptosis, reversed by co-expression of wild-type GRB10. Yeast two-hybrid (MEK1 as bait), random mutagenesis of SH2 domain, co-expression in HTC-IR and COS-7 cells The Journal of biological chemistry Medium 9553107
1998 GRB10 was identified as a regulator of growth hormone (GH) signaling: GRB10 associates with the GH receptor and Jak2 under GH stimulation, and inhibits transcription of SRE- and GH-response element-containing reporter genes but not STAT5-dependent reporters. Modified receptor target cloning procedure, co-transfection co-immunoprecipitation in 293 cells, transcriptional reporter assays in Huh-7 cells The Journal of biological chemistry Medium 9632636
1998 GRB10 was identified as a binding partner of BCR-ABL via its SH2 domain at a Bcr autophosphorylation site distinct from the Grb2 binding site; interaction is kinase-activation-dependent; a BCR-ABL mutant lacking the GRB10 binding site has reduced capacity to induce IL-3 independence and focus formation. Yeast two-hybrid, GST pulldown, co-immunoprecipitation in CML cells, temperature-sensitive BCR-ABL system, transformation assays Oncogene Medium 9747873
1998 GRB10/GrbIR is phosphorylated by the non-receptor tyrosine kinase Tec (but not by Syk, Jak2, or insulin receptor) in a transient expression system; GRB10 expression suppresses Tec-driven activation of the c-fos promoter, acting as a downstream effector/suppressor of Tec signaling. Yeast two-hybrid, transient transfection in HEK293 cells, tyrosine phosphorylation assay, transcriptional reporter assay Genes to cells Medium 9753425
1999 Endogenous GRB10 is predominantly localized to mitochondria (by immunofluorescence and subcellular fractionation); small pools relocate to plasma membrane and actin-rich ruffles after IGF-I or serum treatment; endogenous GRB10 and Raf-1 co-immunoprecipitate from mitochondrial fractions, with interaction enhanced by UV-activated Raf-1, suggesting GRB10 regulates mitochondrial Raf-1 anti-apoptotic activity. Immunofluorescence microscopy, subcellular fractionation, co-immunoprecipitation from mitochondrial extract, yeast two-hybrid mapping The Journal of biological chemistry Medium 10585452
1999 GRB10 functions as a positive stimulatory signaling adapter in PDGF-BB-, IGF-I-, and insulin-mediated mitogenesis; Tyr-771 of PDGFRβ mediates GRB10 SH2 domain association; microinjection and cell-permeable peptide mimetics of the GRB10 SH2 domain inhibit DNA synthesis; overexpression increases cell proliferation. Ecdysone-inducible expression, microinjection, cell-permeable peptide mimetics (antennapedia-fused), DNA synthesis assay, cell number counts Molecular and cellular biology Medium 10454568
2000 GRB10 is phosphorylated on tyrosine (specifically Tyr-67) by Src family kinases (Src and Fyn) but not by the insulin receptor kinase itself; this Src/Fyn-mediated phosphorylation negatively regulates GRB10 binding to the insulin receptor. Pharmacological inhibition (herbimycin A), dominant-negative and constitutively active Src/Fyn expression, purified kinase in vitro assay, site-directed mutagenesis (Y67G), co-immunoprecipitation Oncogene High 10871840
2001 The BPS domain of GRB10 directly inhibits substrate phosphorylation by the activated tyrosine kinase domains of the insulin receptor and IGF-1 receptor in vitro; inhibition depends on activation-loop phosphorylation but the BPS domain does not bind directly to phosphotyrosine. In vitro kinase assay with purified recombinant proteins, peptide competition experiments FEBS letters High 11287005
2001 GRB10 is a positive regulator of VEGF-R2 (KDR) signaling: overexpression of GRB10 increases KDR protein levels and tyrosine phosphorylation and activates MAP kinase; GRB10 undergoes VEGF-induced tyrosine phosphorylation partly through Src, requiring an intact SH2 domain; GRB10's positive effect on KDR is SH2-domain-independent. Transfection in HUVEC and 293 cells, co-immunoprecipitation, mutant expression, immunoblotting Oncogene Medium 11494124
2002 GRB10 inhibits the IRS/PI3K/Akt signaling pathway by physically blocking IRS-1/IRS-2 access to the insulin receptor; overexpression reduces insulin-stimulated IRS-1 and IRS-2 tyrosine phosphorylation and Akt phosphorylation; yeast tri-hybrid studies show GRB10 SH2 domain is required for blocking IRS-IR association; GRB10 does not reduce IR catalytic activity toward activation loop and juxtamembrane tyrosines. Stable overexpression in CHO/IR cells and adipocytes, yeast tri-hybrid, RNAi knockdown, immunoblotting The Journal of biological chemistry High 12493740
2002 GRB10 forms a constitutive complex with Akt; overexpression of GRB10 and c-kit synergistically activates Akt in a wortmannin-sensitive, PI3K-activity-independent manner; both PH and SH2 domains of GRB10 are required for Akt activation; GRB10 can rescue deficient Akt activation by a c-kit mutant lacking the PI3K binding site. Yeast two-hybrid (c-kit as bait), co-immunoprecipitation, overexpression in Ba/F3 cells, kinase assay, IL-3-independence growth assay, domain deletion mutants Molecular and cellular biology Medium 11809791
2003 GRB10 forms a complex with the E3 ubiquitin ligase Nedd4 and the IGF-IR; GRB10 acts as adapter bringing Nedd4 to the IGF-IR, promoting ligand-dependent IGF-IR ubiquitination, increased internalization, and shortened receptor half-life via both proteasomal and lysosomal pathways; the GRB10 SH2 domain is required for this effect. Co-immunoprecipitation (triple complex), overexpression of catalytically inactive Nedd4 mutant, SH2 domain deletion mutant, pulse-chase half-life assay, proteasome/lysosome inhibitors, dansylcadaverine treatment Molecular and cellular biology High 12697834
2003 GRB10 N-terminus interacts with two novel proteins GIGYF1 and GIGYF2 via their GYF domains binding to tandem proline-rich regions in GRB10; IGF-I stimulation increases GIGYF1 binding to GRB10 and transient binding of both to IGF-IR; overexpression of GIGYF1-GRB10-binding fragment increases IGF-I-stimulated receptor tyrosine phosphorylation. Yeast two-hybrid, co-immunoprecipitation, mutation analysis, overexpression in R+ fibroblasts The Journal of biological chemistry Medium 12771153
2003 GRB10 negatively regulates insulin-stimulated MAPK signaling by blocking Shc tyrosine phosphorylation; GRB10 overexpression reduces MAPK and Shc phosphorylation; the inhibitory effect requires the GRB10 SH2 domain; RNAi knockdown of GRB10 enhances MAPK, Shc, and Akt phosphorylation. Overexpression in CHO/IR cells and 3T3-L1 adipocytes, SH2 domain deletion, RNAi knockdown in HeLa/IR cells, immunoblotting Molecular endocrinology Medium 14615605
2003 Mouse GRB10 links the insulin receptor to p85 PI3-kinase directly (without involving IRS proteins), regulating PI3K activity and downstream metabolic insulin responses (glycogen synthesis, glucose/amino acid transport, lipogenesis, Akt/PKB, GSK, and glycogen synthase); dominant-negative GRB10 SH2 domain eliminates metabolic insulin responses in 3T3-L1 adipocytes. Co-immunoprecipitation of GRB10-p85 complex, dominant-negative domain peptides, metabolic assays in differentiated adipocytes and L6 cells The Journal of biological chemistry Medium 12783867
2003 Crystal structure of the GRB10 SH2 domain at 1.65 Å reveals a non-covalent homodimer under physiologic conditions; the dimer interface involves residues flanking the C-terminal alpha helix conserved in the Grb7/10/14 family; structural features (Val-522, Asp-500) favor binding to dimeric phosphotyrosine sequences such as the insulin and IGF-1R activation loops. X-ray crystallography, analytical ultracentrifugation (solution dimerization), structural analysis The Journal of biological chemistry High 12551896
2003 GRB10 disruption in mice (maternal allele) results in ~30% overgrowth of embryo and placenta by an IGF-2-independent mechanism; genetic epistasis with Igf2 mutation shows GRB10 acts on a distinct fetal growth axis. Gene-trap knockout, genetic cross with Igf2 mutant mice (epistasis), body weight measurements Proceedings of the National Academy of Sciences High 12829789
2004 GRB10 constitutively associates with Nedd4 and prevents Nedd4-mediated degradation of VEGF-R2; Nedd4 overexpression causes VEGF-R2 disappearance, but co-expression with GRB10 restores VEGF-R2 levels; VEGF-R2 is ubiquitinated but Nedd4 is not the direct E3 ligase for VEGF-R2 ubiquitination. Co-immunoprecipitation, overexpression of Nedd4 and GRB10 in cells, ubiquitination assay, Nedd4 catalytic mutant (C854S), MG132 treatment The Journal of biological chemistry Medium 15060076
2005 RNAi knockdown of endogenous GRB10 enhances IGF-I-stimulated IRS phosphorylation, Akt/PKB, and ERK1/2, and increases DNA synthesis; GRB10 knockdown paradoxically decreases IGF-IR autophosphorylation, an effect partially reversed by phosphatase inhibitor pervanadate, suggesting GRB10 protects the activated receptor from phosphatases. siRNA knockdown, immunoblotting of downstream signaling, DNA synthesis assay, pervanadate pretreatment Endocrinology Medium 16037382
2005 Transgenic overexpression of Meg1/Grb10 in mice causes postnatal growth retardation and hyperinsulinemic insulin resistance in vivo, confirming that GRB10 negatively regulates both IGF1R- and IR-dependent signaling pathways in vivo. Transgenic mouse lines (4 independent lines), glucose tolerance test, insulin tolerance test, body weight measurement Biochemical and biophysical research communications High 15752742
2005 Phosphorylation of GRB10 (at Ser-428) by Akt creates a binding site for 14-3-3 proteins; Akt directly binds GRB10 and phosphorylates it in vitro; only the phosphorylated form of GRB10 co-immunoprecipitates with endogenous 14-3-3. Yeast two-hybrid (14-3-3 as binding partner), co-immunoprecipitation, in vitro Akt kinase assay, site-directed mutagenesis (S428A) The Journal of biological chemistry High 15722337
2006 GRB10 mediates insulin-stimulated proteasomal degradation of the insulin receptor; suppression of GRB10 by RNAi leads to increased IR protein levels and reduced insulin-stimulated IR ubiquitination; overexpression reduces IR levels without affecting IR mRNA; IR reduction is blocked by MG132 but not chloroquine. RNAi knockdown, stable overexpression, qRT-PCR (mRNA unchanged), ubiquitination assay, proteasome/lysosome inhibitors American journal of physiology. Endocrinology and metabolism High 16434550
2007 Peripheral (maternal allele) knockout of Grb10 in mice leads to enhanced insulin-stimulated Akt and MAPK phosphorylation in skeletal muscle and fat, and increased whole-body insulin sensitivity by hyperinsulinemic-euglycemic clamp, establishing GRB10 as an in vivo negative regulator of insulin signaling. Gene-trap knockout mice (maternal inheritance), hyperinsulinemic-euglycemic clamp, insulin-stimulated kinase phosphorylation in tissues Molecular and cellular biology High 17620412
2007 Grb10-deficient (Grb10Δ2-4) mice show improved glucose tolerance and insulin sensitivity, and tissue-specific changes in IR tyrosine phosphorylation consistent with GRB10 blocking phosphatase access to IR activation loop; IRS-1 tyrosine phosphorylation is also enhanced, supporting attenuation of IR→IRS-1 signal transmission. Knockout mouse (Grb10Δ2-4), glucose and insulin tolerance tests, tissue IR phosphorylation analysis, IRS-1 phosphorylation assay Molecular and cellular biology High 17562854
2007 GRB10 and active Raf-1 promote Bad-dependent cell survival; both Grb10 and Raf-1 knockout cells show enhanced apoptosis in response to Bad; GRB10 requires its SH2, proline-rich, and PH domains plus Akt phosphorylation site (and consequent 14-3-3 binding) for anti-apoptotic function; Raf-1 requires its kinase activity and Ras-associated domain binding to GRB10 SH2. Knockout MEFs (Grb10 and Raf-1 deficient), siRNA, mutagenesis of GRB10 domains, signaling inhibitors, kinase assays The Journal of biological chemistry Medium 17535812
2007 GRB10 interacts with the Wnt co-receptor LRP6 intracellular domain and negatively regulates canonical Wnt signaling; GRB10 overexpression attenuates Wnt3a-induced β-catenin accumulation and TCF reporter activity; GRB10 interferes with Axin binding to LRP6; RNAi knockdown of GRB10 stimulates Wnt signaling. Co-immunoprecipitation of GRB10-LRP6, TCF reporter assays, RNAi knockdown, β-catenin accumulation assay, Axin binding competition assay Biochemical and biophysical research communications Medium 17376403
2008 The GRB10/Nedd4 complex mediates multiubiquitination (not polyubiquitination) of the IGF-IR upon ligand stimulation, which is required for receptor internalization; GRB10 and Nedd4 associate with IGF-IR in early endosomes and caveosomes but are not degraded and are directed to recycling endosomes. Ubiquitin chain analysis, clathrin-dependent and -independent internalization assays, confocal microscopy, subcellular fractionation, co-immunoprecipitation from endosomal fractions Journal of cellular physiology Medium 18286479
2009 Crystal structure of the Grb10 RA-PH tandem domain at 2.6 Å reveals an integrated dimeric structural unit (RA+PH+linker); biochemical studies show Grb14 (family member) binds activated Ras via its RA domain; these domains illuminate membrane-recruitment mechanisms shared with MIG-10, RIAM, lamellipodin, and Pico. X-ray crystallography, biochemical binding assays for Ras interaction Nature structural & molecular biology High 19648926
2010 Crystal structure of the NEDD4 C2 domain – GRB10 SH2 domain complex at 2.0 Å shows three interaction interfaces, with the main interface being an antiparallel β-sheet; NEDD4 C2 binds at non-classical sites on the SH2 surface far from the phosphotyrosine pocket (phosphotyrosine-independent); GRB10 SH2 can simultaneously bind NEDD4 C2 and IGF-1R kinase domain. X-ray crystallography, structural analysis, binding interface characterization The Journal of biological chemistry High 20980250
2011 mTORC1-mediated phosphorylation of GRB10 stabilizes GRB10 protein, leading to feedback inhibition of both the PI3K and ERK-MAPK pathways; identified by large-scale quantitative phosphoproteomics as a direct mTORC1 substrate. Quantitative phosphoproteomics (large-scale), mTORC1 substrate characterization, rapamycin treatment, loss-of-function experiments Science High 21659605
2011 Within the brain, Grb10 is expressed from the paternal allele; ablation of paternal Grb10 specifically increases social dominance behavior in mice; maternal allele ablation causes peripheral overgrowth—demonstrating tissue-specific allelic function controlling distinct physiological processes. Allele-specific knockout mice, behavioral testing (social dominance, allogrooming), body weight measurement Nature High 21270893
2012 GRB10 deletion in mice increases myofiber number (not fiber size) in skeletal muscle; the hypermuscular phenotype originates during embryonic development; Grb10-deficient neonatal muscle shows upregulated functional gene signatures for myogenic signaling and proliferation. Grb10 knockout mice, histomorphometry (fiber number and cross-sectional area), neonatal limb measurements, gene expression profiling FASEB journal Medium 22623587
2012 GRB10 physically associates with FLT3 at phospho-tyrosines 572 and 793 in a ligand-dependent manner, and constitutively with oncogenic FLT3-ITD; GRB10 enhances FLT3-induced Akt phosphorylation by directly interacting with p85 PI3K subunit; GRB10 depletion reduces Akt phosphorylation. Co-immunoprecipitation, receptor phosphorylation site mapping (Y572F/Y793F mutants), p85 pulldown, siRNA knockdown, cell proliferation and colony formation assays Molecular oncology Medium 23246379
2014 mTOR-mediated phosphorylation of GRB10 at Ser501/503 switches its binding preference from the insulin receptor to raptor (mTOR complex component), leading to raptor-mTOR dissociation and mTORC1 downregulation; fat-specific GRB10 disruption increases mTORC1 signaling, suppresses lipolysis, and reduces thermogenesis; these effects are abolished by rapamycin. mTORC1 substrate phosphorylation assay (Ser501/503), co-immunoprecipitation of GRB10-raptor complex, fat-specific Grb10 knockout mice, in vivo rapamycin treatment, lipolysis assay, thermogenic gene expression Cell metabolism High 24746805
2014 GRB10 associates with IRS-2, NEDD4.2, IL-4Rα, and γc after IL-4 stimulation in macrophages; GRB10 knockdown enhances Tyr(P)-IRS-2 and promotes M2 macrophage gene expression (CD200R, CCL22, MMP12, TGM2); IL-4Rα and γc are ubiquitinated after IL-4 treatment, suggesting GRB10 regulates IL-4 receptor complex degradation through NEDD4.2. Co-immunoprecipitation, siRNA knockdown, ubiquitination assay, M2 gene expression analysis The Journal of biological chemistry Medium 27742835
2016 Deletion of the maternal allele of Grb10 in mice substantially increases hematopoietic stem cell (HSC) long-term repopulating capacity and accelerates HSC regeneration after irradiation; enhanced HSC regeneration is dependent on activation of the Akt/mTORC1 pathway; Grb10-deficient HSCs show increased proliferation with upregulation of CDK4 and Cyclin E. Maternal allele-specific Grb10 knockout mice, competitive transplantation, total body irradiation, flow cytometry, pathway inhibitor studies (Akt/mTORC1), cell cycle marker analysis Cell reports Medium 27806297
2018 Ablation of Grb10 specifically in muscle (muscle-specific KO using α-skeletal actin-Cre) is sufficient to enlarge muscle fibers and increase insulin-stimulated glucose uptake and phospho-Akt in muscle, confirming a cell-autonomous role of GRB10 as modulator of proximal insulin receptor signaling in muscle. Muscle-specific conditional knockout (Cre-lox), hyperinsulinemic-euglycemic clamp, immunoblotting of insulin signaling Endocrinology High 29370381
2018 GRB10 expression is silenced in adult mouse liver but can be reactivated by acute ER stress (tunicamycin or short-term high-fat diet) via ATF4-mediated transcriptional induction; liver-specific GRB10 KO suppresses lipogenic gene expression and ER-stress-induced hepatosteatosis, establishing GRB10 as a mediator of acute ER stress-induced hepatic lipid dysregulation. Liver-specific GRB10 knockout, ER stress induction (tunicamycin, HFD), ATF4 ChIP/transcription analysis, lipogenic gene expression, hepatic lipid assays Journal of molecular endocrinology Medium 29555819
2019 mTORC1 phosphorylates GRB10 at Ser476 in human skeletal muscle cells; insulin and amino acids independently and additively stimulate this phosphorylation; mTORC1 controls PI3K/Akt signaling through GRB10-mediated modulation of insulin receptor protein abundance; rapamycin blocks Grb10 Ser476 phosphorylation and reduces GRB10 protein levels with corresponding increase in IR. Grb10 knockdown in primary human myotubes, rapamycin treatment, phospho-Ser476 immunoblotting, glucose uptake assay, IR protein quantification American journal of physiology. Endocrinology and metabolism Medium 31794259
2023 GRB10 in hypothalamic AgRP and POMC neurons interacts with the leptin receptor and enhances leptin signaling; GRB10 ablation in AgRP neurons promotes weight gain while overexpression reduces body weight; GRB10 in AgRP neurons enhances leptin inhibition via ATP-sensitive K+ channels and in POMC neurons via transient receptor potential channels. Neuron-specific conditional knockout and overexpression (AAV-mediated), electrophysiology (patch-clamp), co-immunoprecipitation of GRB10-leptin receptor, body weight and food intake measurements Nature metabolism High 36593271

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science (New York, N.Y.) 707 21659605
2003 Disruption of the imprinted Grb10 gene leads to disproportionate overgrowth by an Igf2-independent mechanism. Proceedings of the National Academy of Sciences of the United States of America 219 12829789
2003 The Grb10/Nedd4 complex regulates ligand-induced ubiquitination and stability of the insulin-like growth factor I receptor. Molecular and cellular biology 204 12697834
2011 Distinct physiological and behavioural functions for parental alleles of imprinted Grb10. Nature 156 21270893
2000 Human GRB10 is imprinted and expressed from the paternal and maternal allele in a highly tissue- and isoform-specific fashion. Human molecular genetics 142 10861285
2014 A central role for GRB10 in regulation of islet function in man. PLoS genetics 140 24699409
2005 Grb10 and Grb14: enigmatic regulators of insulin action--and more? The Biochemical journal 138 15901248
1995 The cloning of Grb10 reveals a new family of SH2 domain proteins. Oncogene 138 7731717
1996 Ligand activation of ELK receptor tyrosine kinase promotes its association with Grb10 and Grb2 in vascular endothelial cells. The Journal of biological chemistry 137 8798570
1998 Identification of the Meg1/Grb10 imprinted gene on mouse proximal chromosome 11, a candidate for the Silver-Russell syndrome gene. Proceedings of the National Academy of Sciences of the United States of America 134 9448292
1996 Interaction of a GRB-IR splice variant (a human GRB10 homolog) with the insulin and insulin-like growth factor I receptors. Evidence for a role in mitogenic signaling. The Journal of biological chemistry 128 8798417
1998 Grb10 interacts differentially with the insulin receptor, insulin-like growth factor I receptor, and epidermal growth factor receptor via the Grb10 Src homology 2 (SH2) domain and a second novel domain located between the pleckstrin homology and SH2 domains. The Journal of biological chemistry 121 9506989
1995 The Ret receptor protein tyrosine kinase associates with the SH2-containing adapter protein Grb10. The Journal of biological chemistry 121 7665556
2003 Conserved methylation imprints in the human and mouse GRB10 genes with divergent allelic expression suggests differential reading of the same mark. Human molecular genetics 120 12700169
2000 Duplication of 7p11.2-p13, including GRB10, in Silver-Russell syndrome. American journal of human genetics 117 10631135
2004 Grb10 prevents Nedd4-mediated vascular endothelial growth factor receptor-2 degradation. The Journal of biological chemistry 113 15060076
2007 Peripheral disruption of the Grb10 gene enhances insulin signaling and sensitivity in vivo. Molecular and cellular biology 112 17620412
2007 Mice with a disruption of the imprinted Grb10 gene exhibit altered body composition, glucose homeostasis, and insulin signaling during postnatal life. Molecular and cellular biology 109 17562854
1997 Human GRB-IRbeta/GRB10. Splice variants of an insulin and growth factor receptor-binding protein with PH and SH2 domains. The Journal of biological chemistry 105 9006901
1996 Evidence for the direct interaction of the insulin-like growth factor I receptor with IRS-1, Shc, and Grb10. Molecular endocrinology (Baltimore, Md.) 105 8776723
2014 Grb10 promotes lipolysis and thermogenesis by phosphorylation-dependent feedback inhibition of mTORC1. Cell metabolism 102 24746805
2002 Grb10 inhibits insulin-stimulated insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase/Akt signaling pathway by disrupting the association of IRS-1/IRS-2 with the insulin receptor. The Journal of biological chemistry 98 12493740
1998 Interaction of the Grb10 adapter protein with the Raf1 and MEK1 kinases. The Journal of biological chemistry 98 9553107
2003 Two novel proteins that are linked to insulin-like growth factor (IGF-I) receptors by the Grb10 adapter and modulate IGF-I signaling. The Journal of biological chemistry 97 12771153
2003 Imprinting regulation of the murine Meg1/Grb10 and human GRB10 genes; roles of brain-specific promoters and mouse-specific CTCF-binding sites. Nucleic acids research 95 12595547
1999 Grb10, a positive, stimulatory signaling adapter in platelet-derived growth factor BB-, insulin-like growth factor I-, and insulin-mediated mitogenesis. Molecular and cellular biology 95 10454568
1996 Interaction between the Grb10 SH2 domain and the insulin receptor carboxyl terminus. The Journal of biological chemistry 90 8621530
2008 Grb10/Nedd4-mediated multiubiquitination of the insulin-like growth factor receptor regulates receptor internalization. Journal of cellular physiology 87 18286479
1999 Duplication of 7p12.1-p13, including GRB10 and IGFBP1, in a mother and daughter with features of Silver-Russell syndrome. Human genetics 87 10987657
1997 The adapter protein Grb10 associates preferentially with the insulin receptor as compared with the IGF-I receptor in mouse fibroblasts. The Journal of clinical investigation 87 9062339
2002 Role for the adaptor protein Grb10 in the activation of Akt. Molecular and cellular biology 82 11809791
1999 Localization of endogenous Grb10 to the mitochondria and its interaction with the mitochondrial-associated Raf-1 pool. The Journal of biological chemistry 77 10585452
2009 Maternally-inherited Grb10 reduces placental size and efficiency. Developmental biology 75 19833122
2001 The BPS domain of Grb10 inhibits the catalytic activity of the insulin and IGF1 receptors. FEBS letters 75 11287005
1996 Grb10: A new substrate of the insulin-like growth factor I receptor. Cancer research 74 8764099
2000 Imprinting of human GRB10 and its mutations in two patients with Russell-Silver syndrome. American journal of human genetics 73 10856193
2005 Meg1/Grb10 overexpression causes postnatal growth retardation and insulin resistance via negative modulation of the IGF1R and IR cascades. Biochemical and biophysical research communications 67 15752742
2008 A mono-allelic bivalent chromatin domain controls tissue-specific imprinting at Grb10. The EMBO journal 66 18650936
2009 Structural and functional studies of the Ras-associating and pleckstrin-homology domains of Grb10 and Grb14. Nature structural & molecular biology 64 19648926
2013 Regulation of insulin and type 1 insulin-like growth factor signaling and action by the Grb10/14 and SH2B1/B2 adaptor proteins. The FEBS journal 63 23190452
2009 Paternal deletion of Meg1/Grb10 DMR causes maternalization of the Meg1/Grb10 cluster in mouse proximal Chromosome 11 leading to severe pre- and postnatal growth retardation. Human molecular genetics 63 19174477
2005 The adapter protein GRB10 is an endogenous negative regulator of insulin-like growth factor signaling. Endocrinology 62 16037382
1998 Grb10 identified as a potential regulator of growth hormone (GH) signaling by cloning of GH receptor target proteins. The Journal of biological chemistry 62 9632636
2009 Reciprocal imprinting of human GRB10 in placental trophoblast and brain: evolutionary conservation of reversed allelic expression. Human molecular genetics 61 19487367
2018 Circular RNA GRB10 as a competitive endogenous RNA regulating nucleus pulposus cells death in degenerative intervertebral disk. Cell death & disease 57 29476072
2004 Grb10: more than a simple adaptor protein. Frontiers in bioscience : a journal and virtual library 55 14766376
2003 Negative regulation of insulin-stimulated mitogen-activated protein kinase signaling by Grb10. Molecular endocrinology (Baltimore, Md.) 54 14615605
2001 Maternal repression of the human GRB10 gene in the developing central nervous system; evaluation of the role for GRB10 in Silver-Russell syndrome. European journal of human genetics : EJHG 54 11313740
2021 Circ_0009910 shuttled by exosomes regulates proliferation, cell cycle and apoptosis of acute myeloid leukemia cells by regulating miR-5195-3p/GRB10 axis. Hematological oncology 52 33969901
2003 Structural basis for dimerization of the Grb10 Src homology 2 domain. Implications for ligand specificity. The Journal of biological chemistry 51 12551896
2014 Tissue-specific regulation and function of Grb10 during growth and neuronal commitment. Proceedings of the National Academy of Sciences of the United States of America 50 25368187
2006 Role of DNA methylation and histone H3 lysine 27 methylation in tissue-specific imprinting of mouse Grb10. Molecular and cellular biology 46 17101788
1998 The SH2-containing adapter protein GRB10 interacts with BCR-ABL. Oncogene 46 9747873
2009 Dual ablation of Grb10 and Grb14 in mice reveals their combined role in regulation of insulin signaling and glucose homeostasis. Molecular endocrinology (Baltimore, Md.) 45 19541746
2006 Grb10 mediates insulin-stimulated degradation of the insulin receptor: a mechanism of negative regulation. American journal of physiology. Endocrinology and metabolism 45 16434550
2004 Grb10 exceeding the boundaries of a common signaling adapter. Frontiers in bioscience : a journal and virtual library 42 14766395
2014 Developmental programming mediated by complementary roles of imprinted Grb10 in mother and pup. PLoS biology 41 24586114
2012 FLT3 signals via the adapter protein Grb10 and overexpression of Grb10 leads to aberrant cell proliferation in acute myeloid leukemia. Molecular oncology 41 23246379
2003 Growth factor receptor-binding protein 10 (Grb10) as a partner of phosphatidylinositol 3-kinase in metabolic insulin action. The Journal of biological chemistry 41 12783867
2000 Identification of Grb10 as a direct substrate for members of the Src tyrosine kinase family. Oncogene 38 10871840
2015 Carrageenan Inhibits Insulin Signaling through GRB10-mediated Decrease in Tyr(P)-IRS1 and through Inflammation-induced Increase in Ser(P)307-IRS1. The Journal of biological chemistry 37 25784556
2015 Drosophila Gyf/GRB10 interacting GYF protein is an autophagy regulator that controls neuron and muscle homeostasis. Autophagy 37 26086452
1998 Grb10/GrbIR as an in vivo substrate of Tec tyrosine kinase. Genes to cells : devoted to molecular & cellular mechanisms 36 9753425
2007 Genomic imprinting of Dopa decarboxylase in heart and reciprocal allelic expression with neighboring Grb10. Molecular and cellular biology 35 17967881
2000 Grb10 proteins in insulin-like growth factor and insulin receptor signaling (review). International journal of molecular medicine 35 10639593
2001 The adapter protein, Grb10, is a positive regulator of vascular endothelial growth factor signaling. Oncogene 34 11494124
2001 Evidence against GRB10 as the gene responsible for Silver-Russell syndrome. Biochemical and biophysical research communications 34 11527390
2012 Grb10 regulates the development of fiber number in skeletal muscle. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 33 22623587
2016 The TORC1-activated Proteins, p70S6K and GRB10, Regulate IL-4 Signaling and M2 Macrophage Polarization by Modulating Phosphorylation of Insulin Receptor Substrate-2. The Journal of biological chemistry 32 27742835
2020 The circular RNA circ-GRB10 participates in the molecular circuitry inhibiting human intervertebral disc degeneration. Cell death & disease 31 32792505
2016 Amelioration of Diabetic Mouse Nephropathy by Catalpol Correlates with Down-Regulation of Grb10 Expression and Activation of Insulin-Like Growth Factor 1 / Insulin-Like Growth Factor 1 Receptor Signaling. PloS one 30 26986757
2003 Grb10 adapter protein as regulator of insulin-like growth factor receptor signaling. Journal of cellular physiology 30 14566960
2009 Brain-derived neurotrophic factor modulation of Kv1.3 channel is disregulated by adaptor proteins Grb10 and nShc. BMC neuroscience 29 19166614
2007 Grb10 and active Raf-1 kinase promote Bad-dependent cell survival. The Journal of biological chemistry 29 17535812
2023 Hypothalamic Grb10 enhances leptin signalling and promotes weight loss. Nature metabolism 28 36593271
2017 Effect of vitrification on in vitro development and imprinted gene Grb10 in mouse embryos. Reproduction (Cambridge, England) 25 28696244
2022 Tissue-specific Grb10/Ddc insulator drives allelic architecture for cardiac development. Molecular cell 24 36108632
2005 Distinct Grb10 domain requirements for effects on glucose uptake and insulin signaling. Molecular and cellular endocrinology 24 15664450
2014 Grb10 is a dual regulator of receptor tyrosine kinase signaling. Molecular biology reports 23 24420853
2014 Grb10 deletion enhances muscle cell proliferation, differentiation and GLUT4 plasma membrane translocation. Journal of cellular physiology 23 24664951
2023 RILP inhibits tumor progression in osteosarcoma via Grb10-mediated inhibition of the PI3K/AKT/mTOR pathway. Molecular medicine (Cambridge, Mass.) 21 37789274
2016 Deletion of the Imprinted Gene Grb10 Promotes Hematopoietic Stem Cell Self-Renewal and Regeneration. Cell reports 21 27806297
2015 Placental expression of the insulin receptor binding protein GRB10: Relation to human fetoplacental growth and fetal gender. Placenta 21 26390806
2014 Antagonistic roles in fetal development and adult physiology for the oppositely imprinted Grb10 and Dlk1 genes. BMC biology 21 25551289
2010 Structural basis for the interaction between the growth factor-binding protein GRB10 and the E3 ubiquitin ligase NEDD4. The Journal of biological chemistry 21 20980250
2018 Ablation of Grb10 Specifically in Muscle Impacts Muscle Size and Glucose Metabolism in Mice. Endocrinology 20 29370381
2018 De-silencing Grb10 contributes to acute ER stress-induced steatosis in mouse liver. Journal of molecular endocrinology 20 29555819
2014 Negative regulation of Grb10 Interacting GYF Protein 2 on insulin-like growth factor-1 receptor signaling pathway caused diabetic mice cognitive impairment. PloS one 20 25268761
2012 Lentivirus shRNA Grb10 targeting the pancreas induces apoptosis and improved glucose tolerance due to decreased plasma glucagon levels. Diabetologia 20 22222503
2012 Lmx1a is an activator of Rgs4 and Grb10 and is responsible for the correct specification of rostral and medial mdDA neurons. The European journal of neuroscience 20 23106268
2007 GRB10 binds to LRP6, the Wnt co-receptor and inhibits canonical Wnt signaling pathway. Biochemical and biophysical research communications 19 17376403
2003 Inhibition of FGF receptor signalling in Xenopus oocytes: differential effect of Grb7, Grb10 and Grb14. FEBS letters 19 12885405
2002 DDC and COBL, flanking the imprinted GRB10 gene on 7p12, are biallelically expressed. Mammalian genome : official journal of the International Mammalian Genome Society 19 12514746
2008 Mitogenic roles of Gab1 and Grb10 as direct cellular partners in the regulation of MAP kinase signaling. Journal of cellular biochemistry 18 18985678
2008 Type 2 diabetes mellitus in a non-obese mouse model induced by Meg1/Grb10 overexpression. Experimental animals 17 18633161
2005 Phosphorylation of grb10 regulates its interaction with 14-3-3. The Journal of biological chemistry 17 15722337
1998 Genomic structure of the gene for the SH2 and pleckstrin homology domain-containing protein GRB10 and evaluation of its role in Hirschsprung disease. Oncogene 17 9881709
2022 circHtra1/miR-3960/GRB10 Axis Promotes Neuronal Loss and Immune Deficiency in Traumatic Brain Injury. Oxidative medicine and cellular longevity 16 35571247
2019 Role of Grb10 in mTORC1-dependent regulation of insulin signaling and action in human skeletal muscle cells. American journal of physiology. Endocrinology and metabolism 16 31794259
2013 Brain-expressed imprinted genes and adult behaviour: the example of Nesp and Grb10. Mammalian genome : official journal of the International Mammalian Genome Society 16 23974804