IRS1 Antibodies

Insulin receptor substrates (IRS) are responsible for several insulin-related activities, such as glucose homeostasis, cell growth, cell transformation, apoptosis, and insulin signal transduction. IRS-1 is a multi-phosphorylated cytoplasmic docking protein involved in the positive regulation of metabolism and proliferation by insulin, IL-4, and other cytokines. The catalytic domain of the insulin receptor is activated upon binding extracellular binding of ligand, resulting in cytoplasmic binding of IRS proteins. IRS is phosphorylated on tyrosine residues, to recruit a variety of Src homology-2 (SH2) domain-containing proteins and activate PI3-kinase, and MAP kinase signaling pathways. When phosphorylated, tyrosine 612 is a pYMxM consensus motif PI3-kinase binding site, which leads to the activation of the PI3K/AKT signaling pathway. Serine/threonine phosphorylation of IRS-1 has been demonstrated to be a negative regulator of insulin signaling and is responsible for its degradation, although IRS-1 degradation pathways are not well understood. IRS-1 has also been shown to be constitutively activated in cancers such as breast cancer, Wilm's tumors, and adrenal cortical carcinomas, thus making IRS-1 phosphorylation and subsequent degradation an attractive therapeutic option. To date there have been four subtypes identified: IRS-1, 2, 3, and 4, with IRS-1 being widely expressed.