The Pleckstrin Homology Domain in Insulin Receptor Substrate-1 Sensitizes Insulin Signaling

• DOI: 10.1074/jbc.270.20.11715
• Publication Date: 2002-07-26T14:58:38Z
• Authors: Martin G. Myers; Timothy C. Grammer; Jennifer Brooks; Erin M. Glasheen; Ling-Mei Wang; Xiao Jian Sun; John Blenis; Jacalyn H. Pierce; Morris F. White
• Keywords: Pleckstrin homology domain; Insulin receptor substrate; IRS1; Phosphotyrosine-binding domain; Homology

The NH2 terminus of insulin receptor substrate-1 (IRS-1) contains a pleckstrin homology (PH) domain. We deleted the PH domain in IRS-1 (IRS-1 delta PH) and expressed mutant Chinese hamster ovary 32D cells. During stimulation, is poorly tyrosine-phosphorylated CHO cells, but undergoes serine/threonine phosphorylation. Similarly, fails to undergo insulin-stimulated tyrosine phosphorylation which uncouples activation phosphatidylinositol 3'-kinase p70s6k from endogenous receptors. Overexpression 32DIR however, restores rescues responses including mitogenesis. Thus, while not required for engagement downstream signals, it one elements that needed sensitive coupling receptors, especially at ordinary levels found most cells tissues.