Pleiotropic insulin signals are engaged by multisite phosphorylation of IRS-1.

• DOI: 10.1128/mcb.13.12.7418
• Publication Date: 2015-10-06T00:37:17Z
• Authors: X J Sun; D L Crimmins; M G Myers; M Miralpeix; M F White
• Keywords: Phosphotyrosine-binding domain; Insulin receptor substrate; GRB10; IRS1; IRS2; GRB2

IRS-1 (insulin receptor substrate 1) is a principal insulin that undergoes tyrosine phosphorylation during stimulation. It contains over 20 potential sites, and we suspect multiple signals are enabled when the activated kinase phosphorylates several of them. Tyrosine-phosphorylated binds specifically to various cellular proteins containing Src homology 2 (SH2) domains (SH2 proteins). We identified some residues undergo insulin-stimulated by purified in intact cells Automated sequencing manual radiosequencing revealed 460, 608, 628, 895, 939, 987, 1172, 1222; additional sites remain be identified. Immobilized SH2 from 85-kDa regulatory subunit (p85 alpha) phosphatidylinositol 3'-kinase bind preferentially tryptic phosphopeptides Tyr(P)-608 Tyr(P)-939. By contrast, domain GRB2 amino-terminal SHPTP2 (Syp) Tyr(P)-895 Tyr(P)-1172, respectively. These results confirm p85 alpha recognizes YMXM motifs suggest prefers phosphorylated YVNI motif, whereas YIDL motif. extend notion multisite docking protein engages downstream elements signal transmission.