University of Illinois Urbana-Champaign

Insulin Receptor Substrate-1 Serine Phosphorylation by a Novel Phosphatidylinositol-3'-Kinase-Associated Serine Kinase Regulates Insulin and Interferon Receptor Signaling

Cengel, Keith Albert

Content Files
9912207.pdf

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https://hdl.handle.net/2142/83649

Description

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
Issue Date
1998
Doctoral Committee Chair(s)
Freund, Gregory G.
Department of Study
Animal Sciences
Discipline
Animal Sciences
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2015-09-25T21:08:37Z
Keyword(s)
Chemistry, Biochemistry
Language
eng
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.
Graduation Semester
1998
Type of Resource
text
Permalink
http://hdl.handle.net/2142/83649

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