Affinage

SH2B1

SH2B adapter protein 1 · UniProt Q9NRF2

Length
756 aa
Mass
79.4 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

SH2B1 is a multivalent cytoplasmic adaptor protein that amplifies receptor tyrosine kinase and JAK-STAT signaling across metabolic, neurotrophic, and developmental contexts. It binds JAK2 constitutively via non-SH2 regions and upon ligand stimulation via its SH2 domain at JAK2 pTyr813, stabilizing an active JAK2 conformation and promoting downstream STAT3/5 and IRS1/2 phosphorylation; it also directly enhances insulin receptor autophosphorylation, assembles JAK2/SH2B1/IRS1-2 ternary complexes that protect IRS proteins from dephosphorylation and ubiquitination, and thereby amplifies PI3K/Akt signaling in multiple tissues including hypothalamus, pancreatic β-cells, liver, muscle, and adipose tissue (PMID:16098827, PMID:15316008, PMID:15314154, PMID:17565041, PMID:19542202, PMID:27217487). Neuronal SH2B1 is the primary mediator of leptin sensitivity and energy homeostasis—controlling a leptin receptor neuron–sympathetic nervous system–brown adipose tissue thermogenic axis—and additionally regulates brain size, aggression circuitry, and cognitive function by modulating NGF/TrkA- and BDNF/TrkB-dependent ERK, Akt, and actin-reorganization pathways, with isoform-specific subcellular targeting (cytoplasm/plasma membrane for β; nucleolus for δ) determining functional output (PMID:17235396, PMID:32251290, PMID:29180441, PMID:35019135, PMID:38434247). In the peripheral nervous system, SH2B1 promotes Schwann cell myelination by maintaining cytohesin-2 phosphorylation and Arf6 activity (PMID:35077201).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1999 High

    Establishing SH2B1 as a TrkA-binding adaptor required for NGF-induced neuronal differentiation answered whether this SH2 protein had neurotrophic signaling functions beyond its known role in cytokine receptor pathways.

    Evidence GST pulldown, co-IP, and dominant-negative SH2 mutant (R555E) blocking neurite outgrowth in PC12 cells

    PMID:10187854

    Open questions at the time
    • The downstream pathway mediating neurite outgrowth was distinct from ERK and remained unidentified
    • Whether SH2B1 acts on TrkA autophosphorylation magnitude was not tested
  2. 1999 Medium

    Demonstrating direct SH2B1γ interaction with the insulin receptor activation loop at pY1146 established SH2B1 as one of the first adaptor proteins binding this specific autophosphorylation site.

    Evidence In vitro binding assays with IR kinase domain mutagenesis

    PMID:10594240

    Open questions at the time
    • Functional consequence of this binding on IR kinase activity was not measured
    • Only in vitro binding without cellular validation
  3. 2000 Medium

    Linking SH2B1β to GH-induced actin reorganization (membrane ruffling) revealed a cytoskeletal effector function distinct from its JAK2 kinase-stimulatory role.

    Evidence Confocal co-localization with F-actin, mutagenesis of SH2 and N-terminal domains, ruffling/pinocytosis assays in 3T3-F442A cells

    PMID:10777618

    Open questions at the time
    • The actin-regulatory intermediates (Rho GTPases, WASP) were not identified
    • In vivo relevance was not tested
  4. 2001 Medium

    Discovering that SH2B1 forms homopentamers/heteropentamers with APS via its N-terminal domain, and that multimerization is required for TrkA activation, established oligomerization as a core mechanistic feature.

    Evidence Biochemical structure-function analysis, co-IP, dominant-negative overexpression, PC12 NGF differentiation

    PMID:11238898

    Open questions at the time
    • Stoichiometry later revised to dimers; pentameric model not independently confirmed
    • Structural basis of multimerization was unresolved
  5. 2004 High

    Identifying JAK2 pTyr813 as the SH2B1 SH2-domain docking site, and showing it is required for SH2B1-mediated JAK2 activation, defined the key phosphoswitch controlling the SH2B1–JAK2 regulatory interaction.

    Evidence 2D phosphopeptide mapping, phospho-specific antibody, Y813F mutagenesis, co-IP, kinase assays

    PMID:15121872

    Open questions at the time
    • How SH2B1 binding at pY813 mechanistically activates the JAK2 kinase domain was not structurally resolved
    • Role of a second, phosphotyrosine-independent binding site was only later characterized
  6. 2004 High

    Demonstrating that SH2B1 assembles a JAK2/SH2B1/IRS1-2 ternary complex via PH and SH2 domains to amplify leptin-stimulated PI3K/Akt signaling established its scaffold function beyond simple kinase activation.

    Evidence GST pulldown, co-IP in LRb-expressing HEK293, mutagenesis, MEF KO reconstitution

    PMID:15316008

    Open questions at the time
    • Relative contribution of scaffold vs. kinase-enhancer function was not separated in vivo
  7. 2004 High

    Showing that SH2B1 directly stimulates insulin receptor autophosphorylation and that global KO causes diabetes-like metabolic syndrome established SH2B1 as a bona fide insulin signaling amplifier with physiological consequence.

    Evidence In vitro IR kinase assays, KO mouse metabolic phenotyping, IRS1/2 and Akt phosphorylation assays

    PMID:15314154

    Open questions at the time
    • Whether the IR-activating and JAK2-activating functions are mechanistically identical was unresolved
  8. 2005 Medium

    Resolving the oligomeric state to dimers and showing that SH2B1 dimers bridge two JAK2 molecules into a transactivating heterotetramer provided a concentration-dependent activation/inhibition model.

    Evidence Yeast two-hybrid, co-IP, kinase assays at varying SH2B1 concentrations

    PMID:15767667

    Open questions at the time
    • In vivo relevance of concentration-dependent inhibition was not tested
    • No structural model of the dimer interface
  9. 2005 High

    Global KO revealing severe obesity, leptin resistance, and metabolic syndrome established SH2B1 as an essential endogenous enhancer of leptin sensitivity.

    Evidence SH2B1 null mice with leptin signaling (JAK2, STAT3, IRS2) and metabolic phenotyping

    PMID:16098827

    Open questions at the time
    • Tissue-specific contributions (neuronal vs. peripheral) were not yet dissected
  10. 2006 High

    Crystal structure of the SH2B1 SH2 domain bound to JAK2 pY813 peptide revealed the structural basis of phosphopeptide specificity and explained preferential JAK2 binding over IR.

    Evidence X-ray crystallography at 2.35 Å resolution with biochemical binding comparisons

    PMID:16824542

    Open questions at the time
    • Full-length SH2B1 structure and mechanism of kinase activation remained unresolved
    • No structure of SH2B1 bound to IR activation loop
  11. 2007 High

    Neuron-specific SH2B1 rescue of the KO obesity phenotype demonstrated that the brain is the primary site of SH2B1's metabolic action, redirecting the field from peripheral tissues.

    Evidence Neuron-specific SH2B1β transgenic rescue on KO background; hypothalamic leptin signaling assays; metabolic phenotyping

    PMID:17235396

    Open questions at the time
    • Which neuronal populations are responsible was not defined
    • Whether peripheral SH2B1 has any independent metabolic role was unclear
  12. 2007 High

    Defining dual JAK2 binding modes—constitutive non-SH2 binding that restrains basal JAK2 and stimulus-dependent SH2/pY813 binding that activates—refined the model of SH2B1 as a bidirectional kinase regulator.

    Evidence Co-IP with JAK2 Y813F, leptin stimulation, IRS1 phosphorylation assays

    PMID:17565041

    Open questions at the time
    • Structural basis of constitutive inhibitory binding was not determined
  13. 2009 High

    Demonstrating that SH2B1's SH2 domain alone is sufficient to activate purified IR in vitro, and that SH2B1 protects IRS proteins from dephosphorylation, established two separable peripheral insulin-sensitizing mechanisms.

    Evidence In vitro reconstituted IR kinase assay with purified SH2B1; in vitro IRS dephosphorylation assay; TgKO mice

    PMID:19542202

    Open questions at the time
    • Identity of the phosphatase(s) antagonized was not determined
  14. 2010 High

    LepR neuron-specific KO revealing abrogated sympathetic nerve activity and BAT thermogenesis established SH2B1 as a critical node in the leptin→SNS→thermogenesis axis.

    Evidence LepR neuron-specific conditional KO, AAV-ablation and overexpression, direct sympathetic nerve recording, BAT thermogenic program assessment

    PMID:32251290

    Open questions at the time
    • Downstream signaling from SH2B1 that specifically activates sympathetic outflow was not identified
    • Whether SH2B1 is required in other hypothalamic neuron types for thermogenesis was untested
  15. 2013 Medium

    Pancreas-specific KO revealing β-cell apoptosis, reduced mass, and impaired PI3K/Akt signaling extended SH2B1's metabolic role to a cell-autonomous β-cell survival and proliferation function.

    Evidence Pancreas-specific conditional KO, HFD metabolic phenotyping, STZ challenge, islet PI3K/Akt assays

    PMID:24150605

    Open questions at the time
    • Whether the insulin receptor or IGF-1 receptor is the relevant upstream kinase in β-cells was not resolved
    • SH2B1 isoform expressed in β-cells was not specified
  16. 2013 Medium

    Showing SH2B1β enhances BDNF/TrkB-mediated ERK and Akt signaling for neurite outgrowth broadened its neurotrophic role beyond NGF/TrkA to include BDNF/TrkB pathways.

    Evidence Overexpression of SH2B1β and mutants in PC12-TrkB and hippocampal cells; MEK and PI3K inhibitors; neurite outgrowth assays

    PMID:24260264

    Open questions at the time
    • Direct TrkB binding by SH2B1 was not demonstrated biochemically
    • In vivo relevance for BDNF signaling was not tested
  17. 2015 Medium

    Identifying the SH2B1β–IRSp53 interaction as a driver of filopodia and dendritic branching revealed an actin-regulatory pathway linking SH2B1 to neuronal morphogenesis beyond kinase amplification.

    Evidence Reciprocal co-IP, confocal co-localization, overexpression in hippocampal/cortical neurons, neurite/filopodia counting

    PMID:25586189

    Open questions at the time
    • Whether this interaction is regulated by neurotrophins was not tested
    • The relevant upstream signal was not defined
  18. 2016 Medium

    Discovery that SH2B1 in a JAK2/IRS2 complex prevents IRS2 ubiquitination linked mTORC1-regulated SH2B1 translation to IRS2 protein stability and β-cell proliferation.

    Evidence 4E-BP2 KO mice, co-IP of ternary complex, IRS2 ubiquitination assay, Akt/p27 signaling

    PMID:27217487

    Open questions at the time
    • The E3 ubiquitin ligase targeting IRS2 was not identified
    • Whether SH2B1 directly blocks ubiquitination or acts indirectly was unclear
  19. 2016 Medium

    Demonstrating SH2B1 interaction with histone H1 and regulation of chromatin marks (H3K4me3, H3K9me3) at specific promoters during myogenesis revealed an unexpected nuclear/chromatin-regulatory function.

    Evidence ChIP for histone marks and MyoD occupancy, co-IP with histone H1, knockdown myotube assays

    PMID:28039048

    Open questions at the time
    • Mechanism by which a cytoplasmic adaptor accesses and modifies chromatin was not elucidated
    • In vivo muscle phenotype of SH2B1 deletion was not reported
  20. 2018 Medium

    Brain-specific KO causing decreased brain weight and pathological aggression, reversed by brain-specific SH2B1 restoration, established SH2B1 as a regulator of brain development and aggression circuits.

    Evidence Global and brain-specific conditional KO, resident-intruder aggression, c-fos mapping in amygdala/PAG, AAV rescue

    PMID:29180441

    Open questions at the time
    • The neurotrophin receptor or signaling pathway mediating brain growth effects was not specified
    • Whether aggression is secondary to brain size reduction was not disentangled
  21. 2019 Medium

    Knockin mice with human obesity-associated PH domain variants (P322S, ΔPR) developing obesity and prenatal lethality established the PH domain as functionally critical and validated human genetic associations mechanistically.

    Evidence PH domain variant knockin mice, metabolic phenotyping, glucose/insulin tolerance testing

    PMID:31439647

    Open questions at the time
    • The molecular mechanism by which PH domain variants impair SH2B1 function (membrane targeting, IRS binding) was not resolved
  22. 2022 Medium

    Identification of SH2B1's role in Schwann cell myelination via cytohesin-2 phosphorylation and Arf6 activation revealed a peripheral nervous system function mechanistically distinct from its kinase-amplifier role.

    Evidence Schwann cell-specific knockdown in vivo, cytohesin-2 Y381F knockin mice, Arf6 activity assays, myelin thickness measurements

    PMID:35077201

    Open questions at the time
    • Whether SH2B1 directly phosphorylates cytohesin-2 or acts via an intermediary kinase was not established
    • Upstream signal triggering this pathway was not identified
  23. 2022 Medium

    Showing SH2B1δ localizes to nucleoli via unique basic regions and that this localization is required for maximal neurite complexity and BDNF-induced gene expression established isoform-specific subcellular compartmentalization as a functional determinant.

    Evidence Isoform-specific overexpression in KO hippocampal neurons, confocal microscopy, nucleolar targeting mutagenesis, BDNF gene expression assays

    PMID:35019135

    Open questions at the time
    • The nucleolar function (ribosome biogenesis, rRNA processing?) of SH2B1δ was not identified
    • Whether nucleolar SH2B1δ interacts with specific nucleolar proteins was not tested
  24. 2023 Medium

    Cell-type-specific KO in hippocampal inhibitory neurons causing cognitive impairment reversed by ERK inhibition revealed SH2B1 restrains ERK signaling in interneurons to support fluid intelligence.

    Evidence Inhibitory vs. excitatory neuron-specific conditional KO, behavioral testing, single-cell transcriptomics, pharmacological ERK rescue

    PMID:38434247

    Open questions at the time
    • The receptor(s) upstream of SH2B1 in inhibitory neurons were not identified
    • How SH2B1 restrains rather than amplifies ERK in this context (opposite to its canonical role) was not mechanistically explained

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include: the full-length structure of SH2B1 and how it simultaneously engages receptors, JAK2, and IRS proteins; the mechanism by which nucleolar SH2B1δ regulates gene expression; and how SH2B1 switches between kinase-activating and kinase-restraining modes in different cell types.
  • No full-length structural model exists
  • Context-dependent switch between positive and negative regulation is unexplained
  • Nucleolar function of SH2B1δ is mechanistically undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0060090 molecular adaptor activity 4
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005730 nucleolus 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-1266738 Developmental Biology 4 R-HSA-1430728 Metabolism 3 R-HSA-112316 Neuronal System 2
Partners
APSHSPA8INSRIRS1IRS2IRSP53JAK2NTRK1
Complex memberships
JAK2/SH2B1/IRS1-2 ternary complex

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 SH2B1 (SH2-B) is an endogenous enhancer of leptin sensitivity that binds JAK2 and promotes leptin-stimulated activation of hypothalamic JAK2, phosphorylation of STAT3 and IRS2; SH2B1 null mice show severely impaired leptin signaling and develop obesity, hyperglycemia, and metabolic syndrome. Genetic knockout mouse model; leptin signaling assays (JAK2 activation, STAT3/IRS2 phosphorylation); cultured cell overexpression with PTP1B inhibition assay Cell metabolism High 16098827
2004 SH2B1 promotes activation of the PI3-kinase pathway in response to leptin by directly binding IRS1 and IRS2 (via its PH and SH2 domains) and mediating formation of a JAK2/SH2B1/IRS1 or IRS2 ternary complex, thereby enhancing leptin-stimulated tyrosine phosphorylation of IRS1/IRS2 and subsequent PI3K/Akt activation. In vitro binding assays (GST pulldown), co-immunoprecipitation in HEK293 cells stably expressing LRb, mutagenesis of SH2B1 binding domains, MEF KO reconstitution The Journal of biological chemistry High 15316008
2004 SH2B1 (SH2-B) directly enhances insulin receptor autophosphorylation and tyrosine phosphorylation of IRS1/IRS2 in an SH2 domain-dependent manner; systemic deletion of SH2-B impairs insulin receptor signaling in liver, muscle, and fat and causes age-dependent hyperinsulinemia, hyperglycemia, and glucose intolerance. Genetic KO mouse; in vitro kinase assays; cultured cell overexpression and KO analysis of IR, IRS1/IRS2 phosphorylation, Akt and ERK1/2 activation Molecular and cellular biology High 15314154
2004 Tyrosine 813 is a site of JAK2 autophosphorylation (identified by 2D phosphopeptide mapping and phospho-specific antibody) that is required for SH2B1β to bind JAK2 and to enhance JAK2 activity and STAT5B phosphorylation; the homologous Tyr785 in JAK3 is similarly autophosphorylated and required for SH2B1β binding. 2D phosphopeptide mapping, phosphospecific antibody, mutagenesis (Y813F), co-immunoprecipitation, kinase activity assays Molecular and cellular biology High 15121872
2007 SH2B1 regulates leptin/JAK2 signaling by dual mechanisms: (1) constitutive binding via non-SH2 domain to non-phosphorylated JAK2 inhibits basal JAK2; (2) leptin-stimulated JAK2 phosphorylation at Tyr813 recruits the SH2 domain of SH2B1 to activate JAK2; additionally, SH2B1 interacts with IRS1 to facilitate IRS1 phosphorylation independent of JAK2 Tyr813. Co-immunoprecipitation, JAK2 Y813F mutagenesis, leptin stimulation assays, IRS1 phosphorylation assays in cultured cells Molecular endocrinology High 17565041
2007 Neuronal SH2B1β specifically expressed in neural tissue is sufficient to correct metabolic disorders (obesity, leptin resistance, insulin resistance, glucose intolerance) in SH2B1 knockout mice and improves hypothalamic JAK2-mediated leptin signaling, demonstrating that neuronal SH2B1 is the primary site of metabolic action. Neuron-specific SH2B1 transgenic rescue crossed onto KO background (TgKO mice); hypothalamic leptin signaling assays; metabolic phenotyping The Journal of clinical investigation High 17235396
2009 Peripheral SH2B1 directly stimulates insulin receptor catalytic activity (demonstrated by in vitro kinase assay with purified SH2B1) and inhibits tyrosine dephosphorylation of IRS-1/IRS-2 by binding to them; the SH2 domain alone is both required and sufficient for insulin receptor activation. In vitro insulin receptor kinase assay with purified SH2B1; in vitro IRS dephosphorylation assay; TgKO mice expressing SH2B1 only in brain; co-immunoprecipitation Diabetes High 19542202
2001 SH2B1 (SH2-B) and APS exist as homopentamers and/or heteropentamers mediated by their N-terminal dimerization domain; SH2-B multimerization is required for enhancing TrkA autophosphorylation magnitude and duration in response to NGF and for TrkA/SH2-B-mediated morphological differentiation of PC12 cells. Biochemical structure-function analysis; co-immunoprecipitation; dominant-negative overexpression; PC12 cell NGF differentiation assays Molecular and cellular biology Medium 11238898
1999 SH2B1β (SH2-Bbeta) is required for NGF-induced neuronal differentiation: it binds to activated TrkA via its SH2 domain, is tyrosyl-phosphorylated in response to NGF, and overexpression of a dominant-negative SH2 domain mutant (R555E) blocks NGF-induced neurite outgrowth in PC12 cells without altering TrkA, Shc, PLCγ phosphorylation or ERK1/2 activation, indicating a novel downstream pathway. GST-fusion pulldown, co-immunoprecipitation, overexpression of wild-type and SH2 domain mutant in PC12 cells, neurite outgrowth assay The Journal of biological chemistry High 10187854
1999 SH2B1 (SH2-Bgamma isoform) interacts specifically with the insulin receptor kinase domain, requiring phosphorylation of Y1146 in the activation loop triple-tyrosine motif, making it one of only two signaling molecules shown to interact directly with this residue. In vitro binding assays with insulin receptor kinase domain, mutagenesis of IR Y1146 Mammalian genome Medium 10594240
2000 SH2B1β (SH2-Bbeta) is required for growth hormone-induced actin reorganization (membrane ruffling and pinocytosis); it co-localizes with filamentous actin in GH-induced membrane ruffles; both SH2 domain-defective and truncation mutants lacking the N-terminus inhibit GH-induced ruffling, acting via a mechanism distinct from JAK2 kinase stimulation. Cell fractionation, confocal microscopy, overexpression of wild-type and mutant SH2B1 in 3T3-F442A cells, membrane ruffling and pinocytosis assays The Journal of biological chemistry Medium 10777618
2001 SH2B1β specifically activates JAK2 (but not JAK1 or JAK3) when overexpressed, while APS negatively regulates JAK2 and JAK1 but not JAK3; both bind and are phosphorylated by JAK kinases, demonstrating isoform- and kinase-specificity of SH2B family regulation. Overexpression in cells, co-immunoprecipitation, kinase activity/phosphorylation assays for JAK1, JAK2, JAK3, STAT5B The Journal of biological chemistry Medium 11751854
2002 SH2B1β binds to FGFR3 via the SH2 domain at FGFR3 phosphotyrosines Tyr-724 and Tyr-760; SH2B1β is tyrosyl-phosphorylated by activated FGFR3 mutants and enhances FGFR3-stimulated STAT5 phosphorylation and nuclear translocation. Yeast two-hybrid screen, co-immunoprecipitation, FGFR3 mutagenesis (Y724, Y760), STAT5 nuclear translocation assay The Journal of biological chemistry Medium 11827956
2004 SH2B1β undergoes constitutive nucleocytoplasmic shuttling; a nuclear export sequence (amino acids 224–233) containing two critical lysines is required for cytoplasmic/membrane localization and for SH2B1β to enhance NGF-induced neurite outgrowth; nuclear-export-defective mutants cannot support differentiation despite normal ERK activation. Leptomycin B treatment, NES deletion/mutation, confocal microscopy in PC12 and COS-7 cells, stable overexpression neurite outgrowth assay Molecular and cellular biology Medium 15082760
1999 NGF stimulates phosphorylation of SH2B1 (SH2-B) on multiple serines/threonines via kinases downstream of MEK (ERKs 1 and 2 phosphorylate SH2Bbeta on Ser-96 in vitro); however, the S96A mutant still supports NGF-induced neurite outgrowth, suggesting additional MEK-downstream sites are involved. In vitro ERK kinase assay, MEK inhibitor PD98059, protein phosphatase 2A treatment, mutagenesis (S96A), NGF-induced differentiation assay The Journal of biological chemistry Medium 10473609
2005 SH2B1 homodimerizes (and forms heterodimers with APS) via a unique N-terminal domain; dimerization brings two SH2 domains to bind two JAK2 pTyr813 sites, creating heterotetrameric JAK2-(SH2B1)2-JAK2 complexes that transactivate JAK2 at low adapter concentrations, but inhibit kinase activity at high concentrations. Yeast two-hybrid, cellular transfection co-immunoprecipitation, kinase activity assays at varying SH2B1/APS concentrations Molecular and cellular biology Medium 15767667
2006 SH2B1 (and APS) bind JAK2 at multiple sites; binding at pTyr813 is essential for SH2B1-mediated JAK2 activation; a phosphoTyr813-independent binding site mediates inhibition; the region 809–811 in JAK2, likely within JH1/JH2 domains, is a critical component of the regulatory region that SH2B1 binding stabilizes into an active conformation. JAK2 truncation and point mutagenesis, in vitro kinase assays, binding assays for multiple JAK2 sites Molecular and cellular biology Medium 16914724
2006 Crystal structure (2.35 Å) of the SH2B1 SH2 domain in complex with the JAK2 pTyr813 phosphopeptide reveals canonical SH2-phosphopeptide binding with specific recognition of glutamate at +1 and hydrophobic at +3 positions; the SH2B1 SH2 domain prefers JAK2 over insulin receptor due to its monomeric state (versus dimeric APS SH2). X-ray crystallography (2.35 Å), biochemical binding assays comparing SH2B1 vs APS SH2 domains Journal of molecular biology High 16824542
2003 SH2B1β is a positive regulator of NGF-mediated Akt/PKB activation in PC12 cells; it enhances and prolongs NGF-induced phosphorylation of Akt on Ser473, leading to increased phosphorylation of GSK-3 and FOXO forkhead transcription factors and their cytoplasmic retention; a dominant-negative SH2 domain mutant blocks these effects. Stable overexpression of SH2Bbeta and R555E mutant in PC12 cells, Akt kinase assays, phospho-Akt/GSK-3/FOXO western blotting, immunolocalization of FKHR The Journal of biological chemistry Medium 14565960
2007 SH2B2β, a novel isoform of SH2B2 lacking an SH2 domain, acts as an endogenous inhibitor of SH2B1: it binds SH2B1 via the dimerization/PH domain and markedly attenuates SH2B1-promoted JAK2 activation, IRS-1 phosphorylation by JAK2, and insulin-stimulated IRS-1 phosphorylation. GST-fusion pulldown in vitro, co-immunoprecipitation in intact cells, JAK2 kinase assays, insulin signaling assays Endocrinology Medium 17204555
2007 SH2B1 (SH2-B) promotes adipocyte differentiation by enhancing insulin/IGF-I receptor signaling through Akt, leading to phosphorylation and nuclear exclusion of Foxo1, thereby increasing PPARγ mRNA levels; PPARγ up-regulation by SH2B1 is blocked by PI3K inhibitors but not MEK inhibitors. Retroviral overexpression and KO MEF differentiation assays, PPARγ mRNA quantification, Akt/Foxo1 phosphorylation assays, PI3K and MEK inhibitor treatments Molecular endocrinology Medium 17312274
2010 Neuronal SH2B1 regulates energy balance by controlling a leptin receptor neuron/sympathetic nervous system (SNS)/brown adipose tissue/thermogenesis axis; LepR neuron-specific deletion of Sh2b1 abrogates leptin-stimulated sympathetic nerve activation and impairs BAT thermogenic programs, causing cold intolerance and progressive degeneration of adipose SNS. LepR neuron-specific conditional KO, adult-onset hypothalamic-specific AAV-ablation, hypothalamic overexpression; sympathetic nerve recording; BAT thermogenesis measurement; metabolic phenotyping Nature communications High 32251290
2010 The SH2 domain of neuronal SH2B1 is required for maintaining normal body weight and glucose metabolism in vivo; SH2 domain-defective mutant (R555E) expressed neuron-specifically in WT mice promotes obesity and insulin resistance in a dominant-negative manner, while the SH2 domain alone (DeltaN503) is insufficient to rescue the KO phenotype, demonstrating N-terminal regions are also required. Three lines of neuron-specific transgenic mice (WT, R555E, DeltaN503) crossed with SH2B1 KO; metabolic phenotyping; glucose/insulin tolerance tests Endocrinology Medium 20484460
2012 SH2B1 associates with the erythropoietin receptor (EPO-R) via its SH2 domain at phosphotyrosines 343 and 401 (pYXXL sequence); SH2B1β preferentially associates with EPO-R over JAK2 in hematopoietic cells; constitutive SH2B1 association with EPO-R is necessary for optimal SH2-dependent recruitment; absence of SH2B1 leads to enhanced EPO-R downstream signaling, indicating SH2B1 is a negative regulator of EPO signaling. COLT screening, co-immunoprecipitation, in vitro mixing assays, SH2 domain mutagenesis, EPO stimulation signaling assays in cells lacking SH2B1 The Journal of biological chemistry Medium 22669948
2013 SH2B1 in pancreatic β-cells promotes β-cell survival and proliferation by enhancing insulin- and IGF-1-stimulated PI3K/Akt activation; pancreas-specific KO mice show increased β-cell apoptosis, decreased proliferation, reduced β-cell mass, and exacerbated glucose intolerance on high-fat diet. Pancreas-specific conditional KO mice; high-fat diet metabolic phenotyping; STZ challenge; β-cell mass histomorphometry; PI3K/Akt signaling assays in INS-1 cells and islets Diabetes Medium 24150605
2013 SH2B1 promotes insulin expression in β-cells by enhancing JAK2 activation of the insulin promoter and increasing Pdx1 expression and Pdx1 recruitment to the insulin promoter; SH2B1 knockdown reduces, and overexpression increases, insulin expression and glucose-stimulated insulin secretion. siRNA knockdown and overexpression in INS-1 832/13 cells; insulin promoter-luciferase assay; chromatin immunoprecipitation (ChIP) for Pdx1; SH2B1-deficient islet analysis Molecular endocrinology Medium 24645678
2015 SH2B1 mediates pathological cardiac hypertrophy by activating the JAK2/STAT3 signaling cascade; cardiac-specific SH2B1 overexpression exacerbates pressure overload-induced hypertrophy, whereas SH2B1 deletion is protective; pharmacological JAK2 inactivation rescues hypertrophic abnormalities in SH2B1-overexpressing transgenic mice. Cardiac-specific SH2B1 transgenic mice and global KO rat model; aortic banding model; echocardiography; JAK2/STAT3 pathway assays; JAK2 inhibitor rescue experiments Cardiovascular research Medium 26077624
2015 SH2B1β interacts with IRSp53 via its N-terminal proline-rich domains; SH2B1-IRSp53 complexes co-localize at the plasma membrane and together promote filopodium formation, neurite initiation, and dendritic branching in hippocampal and cortical neurons. Co-immunoprecipitation in vivo and in vitro, confocal co-localization, Triton X-100 fractionation, overexpression of SH2B1β and IRSp53 in neurons, neurite/filopodia counting The Journal of biological chemistry Medium 25586189
2013 SH2B1 promotes BDNF-induced neurite outgrowth by enhancing MEK-ERK1/2 and PI3K-AKT signaling pathways downstream of TrkB; SH2B1β also enhances BDNF-stimulated STAT3 phosphorylation on Ser727; the SH2 domain and tyrosine phosphorylation of SH2B1β are required for these effects. Overexpression of SH2B1β and mutants in PC12-TrkB and hippocampal cells; pathway inhibitors (MEK, PI3K); neurite outgrowth assays; western blotting of p-ERK, p-AKT, p-STAT3 PloS one Medium 24260264
2018 SH2B1β is phosphorylated by TrkA at Tyr753 in the unique α-tail (and at Tyr439 and Tyr55 shared by α and β isoforms); phosphorylation of Tyr753 in SH2B1α inhibits nucleocytoplasmic cycling and prevents SH2B1α from enhancing NGF-mediated neurite outgrowth, TrkA autophosphorylation, Akt/PLCγ phosphorylation, and gene expression; Y753F mutation restores these functions. Mutagenesis (Y753F and others), co-expression with TrkA, neurite outgrowth assays, western blotting for p-Akt and p-PLCγ, nuclear cycling assays Molecular and cellular biology Medium 29229648
2016 SH2B1 interacts with histone H1 and is required for removal of histone H1 from active transcription sites; SH2B1 promotes histone H3K4me3 induction and H3K9me3 reduction at IGF2 and MYOG promoters/enhancers, is required for MyoD occupancy at these loci, and promotes myogenesis; knockdown delays chromatin condensation and decreases myotube formation. ChIP for histone marks and MyoD occupancy, co-immunoprecipitation with histone H1, SH2B1 knockdown, myotube formation assays Biochimica et biophysica acta. Gene regulatory mechanisms Medium 28039048
2022 SH2B1 promotes myelination in peripheral nervous system Schwann cells by maintaining phosphorylation of cytohesin-2 at Tyr381, which is required for Arf6 activity and normal myelin thickness; Schwann cell-specific loss of SH2B1 reduces cytohesin-2 phosphorylation and myelin thickness; SH2B1 and the phosphatase PTP4A1 act antagonistically to control this phosphorylation. Schwann cell-specific knockdown in mice (in vivo), HEK293T co-expression experiments, Y381F cytohesin-2 knockin mice, Arf6 activity assays, myelin thickness measurements Science signaling Medium 35077201
2022 SH2B1 neuronal protection against MPTP-induced dopaminergic neurodegeneration is mediated by binding to HSC70, which promotes HSC70-dependent recognition and lysosomal translocation/degradation of PLIN4, thereby suppressing lipid peroxidation stress; Sh2b1 deficiency exacerbates PD-like pathology and AAV-HSC70 rescue is effective only in WT but not Sh2b1-deficient mice. MPTP mouse PD model, Sh2b1 KO and neuron-specific overexpression, co-IP of SH2B1-HSC70, PLIN4 degradation assays, AAV-HSC70 rescue, lipid peroxidation measurement Redox biology Medium 35390677
2022 The brain-specific SH2B1δ isoform localizes primarily to nucleoli (driven by two unique highly basic regions) and to the plasma membrane; its nucleolar localization is required for SH2B1δ to maximally enhance neurite complexity and BDNF-induced expression of Egr1, Arc, and FosL1 in hippocampal neurons. Isoform-specific overexpression in Sh2b1 KO hippocampal neurons, confocal microscopy, mutagenesis of nucleolar targeting regions, neurite morphology analysis, BDNF-induced gene expression assays Journal of cell science Medium 35019135
2016 4E-BP2 deletion induces translation of SH2B1, which then forms a complex with IRS2 and JAK2 that prevents IRS2 ubiquitination; this SH2B1-dependent stabilization of IRS2 increases Akt signaling, reduces p27, and promotes β-cell proliferation and survival, linking mTORC1 signaling to IRS2 stability through SH2B1. 4E-BP2 KO mice, co-immunoprecipitation (SH2B1/IRS2/JAK2 complex), IRS2 ubiquitination assay, Akt/p27 signaling assays, cytokine treatment survival assays Diabetes Medium 27217487
2019 The PH domain of SH2B1 is critical for energy balance and glucose homeostasis; mice homozygous for a human obesity-associated P322S PH domain variant show substantial prenatal lethality; mice with a two-amino acid deletion in the PH domain (ΔPR) develop obesity and insulin resistance beyond that attributable to adiposity alone. PH domain variant knockin mouse models (P322S and ΔPR); metabolic phenotyping; glucose and insulin tolerance testing Diabetes Medium 31439647
2017 The SH2 domain of SH2B1 binds diverse phosphotyrosine-containing peptides (JAK2 pY813, insulin receptor activation loop, IRS-1/2) with distinct thermodynamic signatures; residues K575 and R578 play distinct roles in different binding modes; crystal structure reveals conformationally plastic loops enabling recognition of chemically disparate +3 position residues. Binding assays (ITC/fluorescence), X-ray crystallography of SH2B1 SH2 domain, alanine scanning mutagenesis of binding residues Proteins Medium 29127727
2023 Hippocampal SH2B1 in inhibitory (but not excitatory) neurons controls fluid intelligence-related cognitive functions (working memory, short-term recognition memory, behavioral flexibility) by restraining ERK signaling; selective ablation of Sh2b1 in hippocampal inhibitory neurons causes aberrantly enhanced ERK signaling, and pharmacological ERK inhibition reverses associated behavioral impairments. Cell-type-specific conditional KO in mouse hippocampus (inhibitory vs excitatory neurons), behavioral cognitive testing, single-cell transcriptomic profiling, pharmacological ERK inhibitor rescue Research (Washington, D.C.) Medium 38434247
2008 PSM/SH2B1 splice variants (with activity order γ > δ > α > β) enhance Src kinase catalytic activity by increasing V(max) and decreasing K(m) for ATP; SH2B1 variants and Src are found in the same immune complex; SH2B1 also enhances Src-mediated STAT3 activation; dominant-negative PH or SH2 domain peptides inhibit Src activity. Co-immunoprecipitation, in vitro Src kinase assays (V(max)/K(m) measurement), Src inhibitor herbimycin A, dominant-negative peptide mimetics, STAT3 reporter assays Journal of cellular biochemistry Medium 18247337
2018 Neural deletion of Sh2b1 decreases brain weight and increases reactive aggression; brain-specific KO mice show increased c-fos immunoreactivity in amygdala and periaqueductal gray (core aggression circuits); brain-specific restoration of Sh2b1 normalizes brain size and reverses pathological aggression; at the molecular level, Sh2b1 enhances neurotrophin-stimulated neuronal differentiation and protects against oxidative stress-induced neuronal death. Global and brain-specific conditional KO; resident-intruder aggression paradigm; c-fos immunoreactivity mapping; brain-specific AAV restoration; neurotrophin signaling and oxidative stress protection assays FASEB journal Medium 29180441
2020 SH2B1 protects cardiomyocytes from ischemia/reperfusion injury via activation of the PI3K/AKT pathway; adenovirus-mediated SH2B1 overexpression reduces I/R-induced apoptosis, ROS, and inflammation; pharmacological PI3K/AKT inhibition (LY294002) abolishes SH2B1's protective effects. In vivo I/R model (LAD ligation) and in vitro H/R model in cardiomyocytes; adenoviral SH2B1 overexpression; PI3K inhibitor LY294002; apoptosis, ROS, and inflammation assays International immunopharmacology Low 32222636

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Identification of SH2-B as a key regulator of leptin sensitivity, energy balance, and body weight in mice. Cell metabolism 186 16098827
2007 Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. The Journal of clinical investigation 163 17235396
2010 Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity. Genetics in medicine : official journal of the American College of Medical Genetics 150 20808231
2004 SH2-B promotes insulin receptor substrate 1 (IRS1)- and IRS2-mediated activation of the phosphatidylinositol 3-kinase pathway in response to leptin. The Journal of biological chemistry 149 15316008
2012 Human SH2B1 mutations are associated with maladaptive behaviors and obesity. The Journal of clinical investigation 139 23160192
2004 Disruption of the SH2-B gene causes age-dependent insulin resistance and glucose intolerance. Molecular and cellular biology 105 15314154
2004 Tyrosine 813 is a site of JAK2 autophosphorylation critical for activation of JAK2 by SH2-B beta. Molecular and cellular biology 95 15121872
2006 SH2B1 (SH2-B) and JAK2: a multifunctional adaptor protein and kinase made for each other. Trends in endocrinology and metabolism: TEM 94 17140804
2007 SH2B1 enhances leptin signaling by both Janus kinase 2 Tyr813 phosphorylation-dependent and -independent mechanisms. Molecular endocrinology (Baltimore, Md.) 89 17565041
2018 Hsa_circ_0136666 promotes the proliferation and invasion of colorectal cancer through miR-136/SH2B1 axis. Journal of cellular physiology 84 30370521
1999 SH2-B is required for nerve growth factor-induced neuronal differentiation. The Journal of biological chemistry 78 10187854
2016 MicroRNA-361-3p suppresses tumor cell proliferation and metastasis by directly targeting SH2B1 in NSCLC. Journal of experimental & clinical cancer research : CR 77 27164951
2014 SH2B1 regulation of energy balance, body weight, and glucose metabolism. World journal of diabetes 73 25126397
2009 SH2B1 enhances insulin sensitivity by both stimulating the insulin receptor and inhibiting tyrosine dephosphorylation of insulin receptor substrate proteins. Diabetes 72 19542202
2010 Regulation of lifespan, metabolism, and stress responses by the Drosophila SH2B protein, Lnk. PLoS genetics 70 20333234
2001 SH2-B and APS are multimeric adapters that augment TrkA signaling. Molecular and cellular biology 70 11238898
1999 Alternative splicing, gene localization, and binding of SH2-B to the insulin receptor kinase domain. Mammalian genome : official journal of the International Mammalian Genome Society 69 10594240
2009 The Drosophila SH2B family adaptor Lnk acts in parallel to chico in the insulin signaling pathway. PLoS genetics 67 19680438
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
2002 Interaction of fibroblast growth factor receptor 3 and the adapter protein SH2-B. A role in STAT5 activation. The Journal of biological chemistry 59 11827956
2020 Leptin receptor-expressing neuron Sh2b1 supports sympathetic nervous system and protects against obesity and metabolic disease. Nature communications 57 32251290
2005 Kinase activation through dimerization by human SH2-B. Molecular and cellular biology 52 15767667
2002 SH2-B is required for both male and female reproduction. Molecular and cellular biology 52 11940664
2003 Adapter protein with a pleckstrin homology (PH) and an Src homology 2 (SH2) domain (APS) and SH2-B enhance insulin-receptor autophosphorylation, extracellular-signal-regulated kinase and phosphoinositide 3-kinase-dependent signalling. The Biochemical journal 50 12521378
2000 SH2-B is required for growth hormone-induced actin reorganization. The Journal of biological chemistry 48 10777618
2001 SH2-B family members differentially regulate JAK family tyrosine kinases. The Journal of biological chemistry 47 11751854
2010 Effect of FTO, SH2B1, LEP, and LEPR polymorphisms on weight gain associated with antipsychotic treatment. Journal of clinical psychopharmacology 44 21105276
2006 Differential role of SH2-B and APS in regulating energy and glucose homeostasis. Endocrinology 42 16455776
1999 SH2-B, a membrane-associated adapter, is phosphorylated on multiple serines/threonines in response to nerve growth factor by kinases within the MEK/ERK cascade. The Journal of biological chemistry 41 10473609
2007 The SH2B gene is associated with serum leptin and body fat in normal female twins. Obesity (Silver Spring, Md.) 39 17228025
2014 Functional characterization of obesity-associated variants involving the α and β isoforms of human SH2B1. Endocrinology 37 24971614
2010 Critical role of the Src homology 2 (SH2) domain of neuronal SH2B1 in the regulation of body weight and glucose homeostasis in mice. Endocrinology 37 20484460
2007 Identification of SH2B2beta as an inhibitor for SH2B1- and SH2B2alpha-promoted Janus kinase-2 activation and insulin signaling. Endocrinology 36 17204555
2006 Binding of SH2-B family members within a potential negative regulatory region maintains JAK2 in an active state. Molecular and cellular biology 36 16914724
2013 New function of the adaptor protein SH2B1 in brain-derived neurotrophic factor-induced neurite outgrowth. PloS one 35 24260264
2022 BBOX1-AS1 contributes to colorectal cancer progression by sponging hsa-miR-361-3p and targeting SH2B1. FEBS open bio 34 31984680
2001 Functional effects of APS and SH2-B on insulin receptor signalling. Biochemical Society transactions 33 11498022
2012 Mutation screen in the GWAS derived obesity gene SH2B1 including functional analyses of detected variants. BMC medical genomics 31 23270367
2004 Adapter protein SH2-B beta undergoes nucleocytoplasmic shuttling: implications for nerve growth factor induction of neuronal differentiation. Molecular and cellular biology 29 15082760
2000 SH2-B and SIRP: JAK2 binding proteins that modulate the actions of growth hormone. Recent progress in hormone research 29 11036942
2013 SH2B1 in β-cells regulates glucose metabolism by promoting β-cell survival and islet expansion. Diabetes 28 24150605
2007 Adaptor protein SH2-B linking receptor-tyrosine kinase and Akt promotes adipocyte differentiation by regulating peroxisome proliferator-activated receptor gamma messenger ribonucleic acid levels. Molecular endocrinology (Baltimore, Md.) 28 17312274
2006 Structural basis for phosphotyrosine recognition by the Src homology-2 domains of the adapter proteins SH2-B and APS. Journal of molecular biology 28 16824542
2003 SH2-B is a positive regulator of nerve growth factor-mediated activation of the Akt/Forkhead pathway in PC12 cells. The Journal of biological chemistry 28 14565960
2015 SH2B1 is critical for the regulation of cardiac remodelling in response to pressure overload. Cardiovascular research 25 26077624
2013 Hepatic SH2B1 and SH2B2 regulate liver lipid metabolism and VLDL secretion in mice. PloS one 24 24358267
2004 Roles of a conserved family of adaptor proteins, Lnk, SH2-B, and APS, for mast cell development, growth, and functions: APS-deficiency causes augmented degranulation and reduced actin assembly. Biochemical and biophysical research communications 24 14766215
2022 Neuronal SH2B1 attenuates apoptosis in an MPTP mouse model of Parkinson's disease via promoting PLIN4 degradation. Redox biology 22 35390677
2014 Common variants in BDNF, FAIM2, FTO, MC4R, NEGR1, and SH2B1 show association with obesity-related variables in Spanish Roma population. American journal of human biology : the official journal of the Human Biology Council 22 24948161
2011 Computed tomography analysis of the association between the SH2B1 rs7498665 single-nucleotide polymorphism and visceral fat area. Journal of human genetics 22 21796141
2015 SH2B1 and IRSp53 proteins promote the formation of dendrites and dendritic branches. The Journal of biological chemistry 21 25586189
2019 Genome-Wide DNA Methylation Analysis Reveals Epigenetic Pattern of SH2B1 in Chinese Monozygotic Twins Discordant for Autism Spectrum Disorder. Frontiers in neuroscience 20 31379474
2019 Crucial Role of the SH2B1 PH Domain for the Control of Energy Balance. Diabetes 20 31439647
2020 SH2B1 protects cardiomyocytes from ischemia/reperfusion injury via the activation of the PI3K/AKT pathway. International immunopharmacology 19 32222636
2018 Neural deletion of Sh2b1 results in brain growth retardation and reactive aggression. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 19 29180441
2013 The Lnk/SH2B adaptor provides a fail-safe mechanism to establish the Insulin receptor-Chico interaction. Cell communication and signaling : CCS 19 23590848
2013 Screening for coding variants in FTO and SH2B1 genes in Chinese patients with obesity. PloS one 19 23825611
2023 Chromosomal deletions on 16p11.2 encompassing SH2B1 are associated with accelerated metabolic disease. Cell reports. Medicine 18 37586323
2014 SH2B1 CpG-SNP is associated with body weight reduction in obese subjects following a dietary restriction program. Annals of nutrition & metabolism 18 25471250
2012 The joint effect of cigarette smoking and polymorphisms on LRP5, LEPR, near MC4R and SH2B1 genes on metabolic syndrome susceptibility in Taiwan. Molecular biology reports 18 23054017
2011 The SH2B1 obesity locus is associated with myocardial infarction in diabetic patients and with NO synthase activity in endothelial cells. Atherosclerosis 18 21907990
2018 SH2B1 promotes NSCLC cell proliferation through PI3K/Akt/mTOR signaling cascade. Cancer cell international 17 30202243
2012 The SH2B1 adaptor protein associates with a proximal region of the erythropoietin receptor. The Journal of biological chemistry 16 22669948
2019 Distal chromosome 16p11.2 duplications containing SH2B1 in patients with scoliosis. Journal of medical genetics 15 30803986
2018 SH2B1 promotes epithelial-mesenchymal transition through the IRS1/β-catenin signaling axis in lung adenocarcinoma. Molecular carcinogenesis 15 29380446
2011 Replication of the SH2B1 rs7498665 association with obesity in a Belgian study population. Obesity facts 14 22248999
2020 Association of the SH2B1 rs7359397 Gene Polymorphism with Steatosis Severity in Subjects with Obesity and Non-Alcoholic Fatty Liver Disease. Nutrients 13 32365683
2018 SH2B1 protects against OGD/R‑induced apoptosis in PC12 cells via activation of the JAK2/STAT3 signaling pathway. Molecular medicine reports 13 30015896
2014 SH2B1 in β-cells promotes insulin expression and glucose metabolism in mice. Molecular endocrinology (Baltimore, Md.) 13 24645678
2018 The Effect of SH2B1 Variants on Expression of Leptin- and Insulin-Induced Pathways in Murine Hypothalamus. Obesity facts 12 29631267
2016 4E-BP2/SH2B1/IRS2 Are Part of a Novel Feedback Loop That Controls β-Cell Mass. Diabetes 12 27217487
2009 SH2-B beta expression in alveolar macrophages in BAL fluid of asthmatic guinea pigs and its role in NGF-TrkA-mediated asthma. Respirology (Carlton, Vic.) 12 19144050
2020 Hsa_circ_0075960 Serves as a Sponge for miR-361-3p/SH2B1 in Endometrial Carcinoma. Technology in cancer research & treatment 11 33356989
2014 Signaling adaptor protein SH2B1 enhances neurite outgrowth and accelerates the maturation of human induced neurons. Stem cells translational medicine 11 24736401
2008 PSM/SH2B1 splice variants: critical role in src catalytic activation and the resulting STAT3s-mediated mitogenic response. Journal of cellular biochemistry 11 18247337
2019 New perspective on SH2B1: An accelerator of cancer progression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 10 31739166
2017 SH2B1 is Involved in the Accumulation of Amyloid-β42 in Alzheimer's Disease. Journal of Alzheimer's disease : JAD 10 27802221
2017 Discordant phenotypes in monozygotic twins with 16p11.2 microdeletions including the SH2B1 gene. American journal of medical genetics. Part A 10 28544142
2015 Genetic and structural variation in the SH2B1 gene in the Belgian population. Molecular genetics and metabolism 10 26031769
2021 Genetic Obesity in Children: Overview of Possible Diagnoses with a Focus on SH2B1 Deletion. Hormone research in paediatrics 9 34689140
2018 Phosphorylation of the Unique C-Terminal Tail of the Alpha Isoform of the Scaffold Protein SH2B1 Controls the Ability of SH2B1α To Enhance Nerve Growth Factor Function. Molecular and cellular biology 9 29229648
2013 Analyses of non-synonymous obesity risk alleles in SH2B1 (rs7498665) and APOB48R (rs180743) in obese children and adolescents undergoing a 1-year lifestyle intervention. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 9 23519644
2022 The adaptor SH2B1 and the phosphatase PTP4A1 regulate the phosphorylation of cytohesin-2 in myelinating Schwann cells in mice. Science signaling 8 35077201
2022 The nucleolar δ isoform of adapter protein SH2B1 enhances morphological complexity and function of cultured neurons. Journal of cell science 7 35019135
2021 Differential response to a 6-month energy-restricted treatment depending on SH2B1 rs7359397 variant in NAFLD subjects: Fatty Liver in Obesity (FLiO) Study. European journal of nutrition 7 33474638
2013 [Expression of SH2B1 adaptor protein in oesophageal cancer and its clinical significance]. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 7 23456070
2008 Association of genetic variants of MAOA and SH2B1 with bone mineral density in community-dwelling Japanese women. Molecular medicine reports 7 21479408
2002 Association of SH2-B to phosphorylated tyrosine residues in the activation loop of TrkB. Research communications in molecular pathology and pharmacology 7 14632312
2023 SH2B1 Tunes Hippocampal ERK Signaling to Influence Fluid Intelligence in Humans and Mice. Research (Washington, D.C.) 6 38434247
2022 SH2B1 variants as potential causes of non-syndromic monogenic obesity in a Brazilian cohort. Eating and weight disorders : EWD 6 36436143
2014 SH2B1 increases the numbers of IRSp53-induced filopodia. Biochimica et biophysica acta 6 25175559
2014 Implication of SH2B1 gene polymorphism studies in gestational diabetes mellitus in Saudi pregnant women. Saudi journal of biological sciences 6 25473371
2020 Deletion of the Brain-Specific α and δ Isoforms of Adapter Protein SH2B1 Protects Mice From Obesity. Diabetes 5 33214137
2018 Circulating SH2B1 is associated with an increased risk of gastric cancer. Oncology letters 5 29849792
2017 Diversity in peptide recognition by the SH2 domain of SH2B1. Proteins 5 29127727
2015 SH2B1 orchestrates signaling events to filopodium formation during neurite outgrowth. Communicative & integrative biology 5 26479731
2013 The SH2B1 obesity locus and abnormal glucose homeostasis: lack of evidence for association from a meta-analysis in individuals of European ancestry. Nutrition, metabolism, and cardiovascular diseases : NMCD 5 24103803
2016 Evidence for Association between SH2B1 Gene Variants and Glycated Hemoglobin in Nondiabetic European American Young Adults: The Add Health Study. Annals of human genetics 4 27530450
2016 SH2B1 modulates chromatin state and MyoD occupancy to enhance expressions of myogenic genes. Biochimica et biophysica acta. Gene regulatory mechanisms 4 28039048
2025 SH2B1 promotes apoptosis in diabetic cataract via p38 MAPK pathway. iScience 3 39898036