The IRS (Insulin receptor substrate) proteins IRS-1, IRS-2, IRS-3, and IRS-4 are major substrates of the insulin receptor tyrosine kinase and the insulin-like growth factor-1 receptor. IRS proteins contain an N-terminal pleckstrin homology (PH) domain, an ATP-binding domain, and multiple tyrosine phosphorylation sites in the C-terminus. Following insulin receptor ligation, IRS-1 binds to the juxtamembrane region of the receptor and is tyrosine phosphorylated. This facilitates its interaction with SH2 domain-containing signaling proteins, such as PI3 kinase, fyn, Grb2, and PTP1D. Phosphorylation dramatically reduces the affinity of IRS-1 for the insulin receptor, indicating that dissociation from the receptor and subsequent subcellular translocation are important to IRS-1 function in the pleiotropic effects induced by insulin. In support of this, IRS-1-null mice are viable, but exhibit growth retardation and abnormal glucose metabolism. In cases of reduced IRS-1 expression, certain IRS-1 functions can be assumed by the related IRS-2 protein, while other activities linked to IRS-1 are inhibited. Thus, IRS-1 is an essential component of insulin induced signal transduction.
This antibody is routinely tested by western blot analysis. Other applications were tested at BD Bioscience Pharmingen during antibody development only or reported in the literature.