IRS1

Signalling 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. Plays therefore an important role in development, growth, glucose homeostasis as well as lipid metabolism. Upon phosphorylation by the insulin receptor, functions as a signalling scaffold that propagates insulin action through binding to SH2 domain-containing proteins including the p85 regulatory subunit of PI3K, NCK1, NCK2, GRB2 or SHP2. Recruitment of GRB2 leads to the activation of the guanine nucleotide exchange factor SOS1 which in turn triggers the Ras/Raf/MEK/MAPK signalling cascade. 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 signalling pathway through suppression of DVL2 autophagy-mediated degradation leading to cell proliferation. Location: Cytoplasm; Nucleus (UniProt). Locus 2q36.3 (HGNC).