{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/83649"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/83649","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Insulin Receptor Substrate-1 Serine Phosphorylation by a Novel Phosphatidylinositol-3'-Kinase-Associated Serine Kinase Regulates Insulin and Interferon Receptor Signaling","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.","abstract_html":"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.","abstract_has_math":false,"creators":["Cengel, Keith Albert"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Animal Sciences","degree_department":null,"school":null,"contributors":["Freund, Gregory G."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-09-25T21:08:37Z","date_published":"2015-09-25T21:08:37Z","updated_at":"2026-07-22T22:26:21Z","subjects":["Chemistry, Biochemistry"],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["(MiAaPQ)AAI9912207"],"render_values":[{"text":"(MiAaPQ)AAI9912207","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/83649","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Freund, Gregory G."]},{"key":"dc:creator","label":"Author","values":["Cengel, Keith Albert"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2015-09-25T21:08:37Z","1998"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Animal Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Chemistry, Biochemistry"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/83649","(MiAaPQ)AAI9912207"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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). 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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). 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