IRS4: Proteins and Enzymes

IRS4 is a new member of the IRS family, IRS-4, is a 160-kDa tyrosine kinase which phosphorylates cellular substrates when it is activated by the binding of insulin (1). IRS-4 was originally discovered in human embryonic kidney 293 cells. Subcellular fractionation revealed that about 50% of IRS-4 was located in cellular membranes, and immunofluorescence indicated that IRS-4 was concentrated at the plasma membrane. Immunoelectron microscopy conclusively established that a large portion of the IRS-4 was located at the cytoplasmic surface of the plasma membrane in both the unstimulated and insulin-treated states. IRS-4 was found to be associated with two src homology 2 (SH2) domain-containing proteins, phosphatidylinositol 3-kinase and Grb2, the adaptor to the guanine nucleotide exchange factor for Ras (2).