| Background Information | IRS (insulin receptor substrate) is a key mediator of insulin and IGF signaling and is important for cellular functions such as growth, survival, and metabolism. IRS proteins contain no intrinsic enzymatic activity, but rather contribute to signaling through their function as adaptor proteins that serve to recruit effector proteins, such as PI3K, Grb-2, SHP-2, Fyn, c-Crk, CrkII and Nck to tyrosine receptor kinases (IR, IGF1R, VEGFR, EGFR, etc.) as well as other receptors. IRS proteins play an important regulatory function and are associated with various metabolic diseases and cancer.
IRS proteins are phosphorylated on multiple tyrosine sites which serve as docking sites for SH2 containing proteins. Furthermore, IRS signaling is down regulated by serine or threonine phosphorylation, an important mechanism of insulin resistance during acute injury and infection, or chronic stress associated with aging or obesity. IRS can be serine/threonine phosphorylated by various kinases such as Akt, PKC, GSK3, mTOR, JNK, p38, ERK, etc. under conditions of hyperinsulinemia, obesity, inflammation, excess cytokines, lipid accumulation, etc. For example, hyperinsulinemia can lead to phosphorylation of IRS1 on serine 636 by mTOR. Understanding the regulation and signaling by IRS in cell growth, metabolism and survival will lead to new strategies to prevent or cure diabetes and other metabolic diseases.
There are four members of the IRS family. Humans express IRS1, IRS2 and IRS4 while rodents also express Irs3. IRS1 and IRS2 are ubiquitously expressed and are the primary mediators of mitogenic and metabolic effects of insulin/IGF in most cell types. IRS1 and IRS4 are most often associated with tumor growth and proliferation. IRS2 is most often associated with tumor motility and invasion. IRS4 is found primarily in brain, kidney, thymus and liver. The MILLIPLEX® MAP 2-Plex Phospho/Total IRS1 kit detects total IRS1 and phosphorylated IRS1 (Ser636).
The MILLIPLEX® MAP 2-Plex Phospho/Total IRS1 kit contains all the components necessary to measure total IRS1 and phosphorylated IRS1 (Ser636). |
