Recombinant Human IRS2 protein (GST tag N-Terminus)

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 : 25879670). Plays therefore an important role in development, growth, glucose homeostasis as well as lipid metabolism (PubMed : 24616100). 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 : 15316008, PubMed : 19109239). 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). Plays a role in cell cycle progression by promoting a robust spindle assembly checkpoint (SAC) during M-phase (PubMed : 32554797). In macrophages, IL4-induced tyrosine phosphorylation of IRS2 leads to the recruitment and activation of phosphoinositide 3-kinase (PI3K) (PubMed : 19109239).

翻訳後修飾

Phosphorylation fluctuates in a cell-cycle dependent manner with hyperphosphorylation during mitosis (PubMed:32554797). Phosphorylated at Ser-560 and Ser-1109 by PLK1; these phosphorylations prevent the activation of the PI3K pathway upon growth factor stimulation by inhibiting the binding between IRS2 and the PI3K pathway components and increasing the level of IRS2 protein degradation. In addition, they prevent premature mitotic exit (By similarity).. Monoubiquitinated by NEDD4; leading to enhanced IGF1 signaling. During cell cycle, ubiquitination and proteasomal degradation are controlled by FZR1 (PubMed:32554797).