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dc.contributor.authorMohan, Revaen
dc.date2008-11-09 20:53:54.787
dc.date.accessioned2008-11-10T16:22:11Z
dc.date.available2008-11-10T16:22:11Z
dc.date.issued2008-11-10T16:22:11Z
dc.identifier.urihttp://hdl.handle.net/1974/1579
dc.descriptionThesis (Master, Microbiology & Immunology) -- Queen's University, 2008-11-09 20:53:54.787en
dc.description.abstractThe signal transducer and activator of transcription-3 (Stat3) is a latent cytoplasmic protein that is activated through phosphorylation of tyrosine-705 by a number of receptor and non-receptor tyrosine kinases. This leads to Stat3 dimerization by reciprocal SH2-ptyr interactions, followed by translocation to the nucleus to initiate transcription of genes involved in cell growth, survival, and differentiation. Many of these signaling molecules known to activate Stat3 concentrate in specialized plasma membrane microdomains called caveolae, and are sequestered in an inactive state to the caveolin scaffolding domain (CSD) of the main caveolae resident protein, caveolin-1 (cav1). Since many of these signaling molecules are known, potent Stat3 stimulators, we set out to examine the effect of cav1 upon Stat3 activity. To this effect, cav1 was downregulated using a cholesterol chelator (methylcyclodextrin), or an antisense approach. Since we previously found that cell density can dramatically activate Stat3, all experiments were conducted at several densities. The results show that cav1 downregulation causes an increase in Stat3-tyr705 phosphorylation at all densities examined. We next examined the effect of cav1 upregulation upon Stat3 activity by transfecting an EGFP-cav1 construct. The results revealed that cav1 overexpression using this construct reduces Stat3 activity and induces apoptosis, which can be overcome by expression of a constitutively active form of Stat3. Finally, by expressing a Stat3 shRNA with an adenovirus vector, we demonstrated that Stat3 downregulation leads to an increase in cav1 levels. These results reveal the presence of a potent, negative regulatory relationship between cav1 and Stat3 phosphorylation.en
dc.format.extent7817774 bytes
dc.format.mimetypeapplication/pdf
dc.language.isoengen
dc.relation.ispartofseriesCanadian thesesen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.subjectsignal transductionen
dc.subjectcell and molecular biologyen
dc.subjectcell adhesionen
dc.subjectStat3en
dc.subjectcaveolin 1en
dc.subjectconfluenceen
dc.titleRegulation of the signal transducer and activator of transcription-3 by the caveolae protein, caveolin-1en
dc.typethesisen
dc.description.degreeM.Sc.en
dc.contributor.supervisorRaptis, Ledaen
dc.contributor.departmentMicrobiology and Immunologyen
dc.degree.grantorQueen's University at Kingstonen


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