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Freund, Gregory G. Cengel, Keith Albert 2015-09-25T21:08:37Z 2015-09-25T21:08:37Z 1998 1998 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. Made available in DSpace on 2015-09-25T21:08:37Z (GMT). No. of bitstreams: 2 license.txt: 4848 bytes, checksum: 96035ab3f5e1c23cc7138a224ce498bd (MD5) 9912207.pdf: 5384672 bytes, checksum: d7942cf8037673e8ea3c21ee7d71ad18 (MD5) Previous issue date: 1998 Embargo set by: Seth Robbins for item 84930 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs Open 139 p. Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1998. http://hdl.handle.net/2142/83649 (MiAaPQ)AAI9912207 eng Chemistry, Biochemistry Insulin Receptor Substrate-1 Serine Phosphorylation by a Novel Phosphatidylinositol-3'-Kinase-Associated Serine Kinase Regulates Insulin and Interferon Receptor Signaling text Animal Sciences Animal Sciences University of Illinois at Urbana-Champaign Dissertation Ph.D.