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Title:Insulin Receptor Substrate-1 Serine Phosphorylation by a Novel Phosphatidylinositol-3'-Kinase-Associated Serine Kinase Regulates Insulin and Interferon Receptor Signaling
Author(s):Cengel, Keith Albert
Doctoral Committee Chair(s):Freund, Gregory G.
Department / Program:Animal Sciences
Discipline:Animal Sciences
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Chemistry, Biochemistry
Abstract:The data in this thesis demonstrate that phosphatidylinositol 3 '-kinase (PI 3- kinase) associates with a novel serine kinase that can phosphorylate IRS-1 and reduce its ability to act as a substrate for insulin and interferon alpha (IFNalpha) receptors. PI 3-kinase is shown to associate with a wortmannin insensitive 76 kDa serine phosphoprotein (pp76) distinct from the p85 subunit of PI 3-kinase. pp76 is phosphorylated by an okadaic acid sensitive, PI 3-kinase associated serine kinase (PAS kinase) with biochemical properties that distinguish it from the intrinsic serine kinase activity of PI 3-kinase and evidence suggests that PAS kinase may be pp76. PAS kinase associates with the p85 subunit of PI 3-kinase through src homology 2 (SH2) domain interactions and can serine phosphorylate IRS-1 after insulin stimulation. More importantly, PAS kinase mediated IRS-1 serine phosphorylation reduced subsequent tyrosine phosphorylation of IRS-1 by insulin receptors (IRs). Finally, under hyperinsulinernic conditions, IRS-1 serine phosphorylation by PAS kinase can reduce IFNalpha mediated IRS-1 tyrosine phosphorylation. Taken together, these data show that PAS kinase is an IRS-1 serine kinase and that PAS kinase may counter-regulate insulin and cytokine signaling.
Issue Date:1998
Description:139 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1998.
Other Identifier(s):(MiAaPQ)AAI9912207
Date Available in IDEALS:2015-09-25
Date Deposited:1998

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