IRS1 peptide

一般的な情報

機能

Signaling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R (PubMed : 7541045, PubMed : 33991522, PubMed : 38625937). Plays therefore an important role in development, growth, glucose homeostasis as well as lipid metabolism (PubMed : 19639489). Upon phosphorylation by the insulin receptor, functions as a signaling scaffold that propagates insulin action through binding to SH2 domain-containing proteins including the p85 regulatory subunit of PI3K, NCK1, NCK2, GRB2 or SHP2 (PubMed : 11171109, PubMed : 8265614). Recruitment of GRB2 leads to the activation of the guanine nucleotide exchange factor SOS1 which in turn triggers the Ras/Raf/MEK/MAPK signaling cascade (By similarity). Activation of the PI3K/AKT pathway is responsible for most of insulin metabolic effects in the cell, and the Ras/Raf/MEK/MAPK is involved in the regulation of gene expression and in cooperation with the PI3K pathway regulates cell growth and differentiation. Acts a positive regulator of the Wnt/beta-catenin signaling pathway through suppression of DVL2 autophagy-mediated degradation leading to cell proliferation (PubMed : 24616100).

翻訳後修飾

Serine phosphorylation of IRS1 is a mechanism for insulin resistance. Ser-307, Ser-312, Ser-315, and Ser-323 phosphorylations inhibit insulin action through disruption of IRS1 interaction with the insulin receptor INSR (PubMed:38625937). Phosphorylation of Tyr-896 is required for GRB2-binding (By similarity). Phosphorylated by ALK. Phosphorylated at Ser-270, Ser-307, Ser-636 and Ser-1101 by RPS6KB1; phosphorylation induces accelerated degradation of IRS1 (PubMed:18952604). Phosphorylated on tyrosine residues in response to insulin (PubMed:23401856). In skeletal muscles, dephosphorylated on Tyr-612 by TNS2 under anabolic conditions; dephosphorylation results in the proteasomal degradation of IRS1 (PubMed:23401856).. Ubiquitinated by the Cul7-RING(FBXW8) complex in a mTOR-dependent manner, leading to its degradation: the Cul7-RING(FBXW8) complex recognizes and binds IRS1 previously phosphorylated by S6 kinase (RPS6KB1 or RPS6KB2) (PubMed:18498745). Ubiquitinated by TRAF4 through 'Lys-29' linkage; this ubiquitination regulates the interaction of IRS1 with IGFR and IRS1 tyrosine phosphorylation upon IGF1 stimulation (PubMed:33991522).. S-nitrosylation at by BLVRB inhibits its activity.

細胞内局在性

Nucleus