SH2-B-beta 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. Belongs to the SH2B adapter family. Widely expressed with highest levels in skeletal muscle and ovary. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Adaptor/scaffold
Chromosomal Location of Human Ortholog: 1q36
Cellular Component:  cytoplasm; nucleus; plasma membrane
Molecular Function:  protein binding; signaling adaptor activity; transmembrane receptor protein tyrosine kinase adaptor activity
Biological Process:  intracellular signal transduction; lamellipodium assembly; positive regulation of mitotic nuclear division; positive regulation of signal transduction; regulation of DNA biosynthetic process; signal transduction; transmembrane receptor protein tyrosine kinase signaling pathway
Reference #:  Q62985-2 (UniProtKB)
Alt. Names/Synonyms: FceRI gamma-chain-interacting protein SH2-B; SH2 domain-containing protein 1B; Sh2-b; SH2-B PH domain containing signaling mediator 1; SH2-B PH domain-containing signaling mediator 1; Sh2b; SH2B adapter protein 1; Sh2b1; Sh2bpsm1
Gene Symbols: Sh2b1
Molecular weight: 70,931 Da
Basal Isoelectric point: 5.54  Predict pI for various phosphorylation states
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SH2-B-beta

Protein Structure Not Found.


Cross-references to other databases:  STRING  |  Reactome  |  BioGPS  |  Pfam  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene