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The Novel Role of Interleukin-1 Receptor-Associated Kinase 1 in the Signaling Process Controlling Innate Immunity and Inflammation

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dc.contributor.authorFang, Youjiaen
dc.contributor.committeechairLi, Liwuen
dc.contributor.committeememberXing, Jianhuaen
dc.contributor.committeememberLi, Jianyongen
dc.contributor.departmentBiologyen
dc.date.accessioned2014-03-14T20:35:32Zen
dc.date.adate2009-05-29en
dc.date.available2014-03-14T20:35:32Zen
dc.date.issued2009-05-05en
dc.date.rdate2012-03-30en
dc.date.sdate2009-05-07en
dc.description.abstractObesity-induced chronic inflammation plays a key role in the pathogenesis of insulin resistance and the metabolic syndrome. Proinflammatory cytokines can cause insulin resistance in adipose tissue, skeletal muscle and liver by inhibiting insulin signaling transduction. Interleukin-1 receptor-associated kinase-1 (IRAK-1) is a serine/threonine kinase functioning in Toll-like Receptor signaling pathways, and plays an important role in inflammation and immune response. In our studies, we demonstrated that IRAK-1 is involved with the negative regulation of PI3K-Akt dependent signaling pathway induced by insulin and TLR 2&4 agonists. Out data also indicate that IRAK-1 can interact with IRS-1 protein both in vivo and in vitro. The binding sites for the IRAK1-IRS1 biochemical interaction are IRS-1's PH domain and IRAK-1's proline-rich LWPPPP motif. Our studies also indicate that IRAK-1 is involved with the negative regulation of glycogen synthesis through inhibiting PI3K-Akt signaling pathway and thus releasing GSK3β's inhibitory effect on glycogen synthase. Moreover, our studies also suggest that IRAK-1 is involved in the activation of transcription factors CREB and ATF-1 by stimulating CREB-Ser133 and ATF-1 phosphorylation. CREB transcription factor family induces genes involved in cellular metabolism, gene transcription, cell cycle regulation, cell survival, as well as growth factor and cytokine genes. That may partially explain our finding that IRAK-1 may be also involved with cell proliferation and survival pathway.en
dc.description.degreeMaster of Scienceen
dc.identifier.otheretd-05072009-114808en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-05072009-114808/en
dc.identifier.urihttp://hdl.handle.net/10919/32331en
dc.publisherVirginia Techen
dc.relation.haspartthesis1.pdfen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectCREBen
dc.subjectIRS-1en
dc.subjectGSK3βen
dc.subjectinsulin resistanceen
dc.subjectAkten
dc.subjectTLRsen
dc.subjectIRAK-1en
dc.titleThe Novel Role of Interleukin-1 Receptor-Associated Kinase 1 in the Signaling Process Controlling Innate Immunity and Inflammationen
dc.typeThesisen
thesis.degree.disciplineBiologyen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.levelmastersen
thesis.degree.nameMaster of Scienceen

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