Summary

Name SH2B1
Full Name SH2B adapter protein 1
Synonyms Pro-rich, PH and SH2 domain-containing signaling mediator, PSM, SH2 domain-containing protein 1B | KIAA1299, SH2B
Primary ID Q9NRF2
Links - -
Type protein
Relations 8
Pathways B-cell activation, Leptin Signaling
Function Adapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways mediated by Janus kinase (JAK) and receptor tyrosine kinases, including the receptors of insulin (INS), insulin-like growth factor I (IGF1), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), platelet-derived growth factor (PDGF) and fibroblast growth factors (FGFs). In growth hormone (GH) signaling, autophosphorylated ('Tyr-813') JAK2 recruits SH2B1, which in turn is phosphorylated by JAK2 on tyrosine residues. These phosphotyrosines form potential binding sites for other signaling proteins. GH also promotes serine/threonine phosphorylation of SH2B1 and these phosphorylated residues may serve to recruit other proteins to the GHR-JAK2-SH2B1 complexes, such as RAC1. In leptin (LEP) signaling, binds to and potentiates the activation of JAK2 by globally enhancing downstream pathways. In response to leptin, binds simultaneously to both, JAK2 and IRS1 or IRS2, thus mediating formation of a complex of JAK2, SH2B1 and IRS1 or IRS2. Mediates tyrosine phosphorylation of IRS1 and IRS2, resulting in activation of the PI 3-kinase pathway. Acts as positive regulator of NGF-mediated activation of the Akt/Forkhead pathway; prolongs NGF-induced phosphorylation of AKT1 on 'Ser-473' and AKT1 enzymatic activity. Enhances the kinase activity of the cytokine receptor-associated tyrosine kinase JAK2 and of other receptor tyrosine kinases, such as FGFR3 and NTRK1. For JAK2, the mechanism seems to involve dimerization of both, SH2B1 and JAK2. Enhances RET phosphorylation and kinase activity. Isoforms seem to be differentially involved in IGF-I and PDGF-induced mitogenesis (By similarity).

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Relations

Regulator Mechanism target score ℹ
+ SH2B1down-regulates activity img/direct_inhibition.png dephosphorylation BLNK 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:B-cell activation
+ CD22up-regulates activity img/direct-activation.png binding SH2B1 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:B-cell activation
+ SH2B1down-regulates activity img/direct_inhibition.png dephosphorylation CD79A 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:B-cell activation
+ SH2B1down-regulates activity img/direct_inhibition.png dephosphorylation CD79B 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:B-cell activation
+ SH2B1down-regulates activity img/direct_inhibition.png dephosphorylation SYK 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:B-cell activation
+ LEPRup-regulates activity img/direct-activation.png binding SH2B1 0.334
Publications: 1
Pathways:Leptin Signaling
+ SH2B1up-regulates activity img/direct-activation.png binding JAK2 0.691
Publications: 1
Pathways:Leptin Signaling
+ NTRK1up-regulates img/direct-activation.png binding SH2B1 0.538
Publications: 1 Organism: Homo Sapiens