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dc.contributor.authorBrisbin, Sarahen
dc.date2009-02-27 17:09:10.582
dc.date.accessioned2009-11-18T16:07:29Z
dc.date.available2009-11-18T16:07:29Z
dc.date.issued2009-11-18T16:07:29Z
dc.identifier.urihttp://hdl.handle.net/1974/5324
dc.descriptionThesis (Master, Biology) -- Queen's University, 2009-02-27 17:09:10.582en
dc.description.abstractThe Caenorhabditis elegans Eph RTK, VAB-1, has known roles in neuronal and epidermal morphogenesis as well as oocyte maturation through interaction with its ephrin ligands. In humans, Eph receptors are involved in nervous and vascular system development and have been implicated in cancer formation and progression. DAF-18, a C. elegans ortholog of the human tumour suppressor gene, PTEN, has been identified as an interacting partner with the Eph RTK, VAB-1. Mutations in human PTEN have been associated with numerous cancers and in the worm, DAF-18 is a well studied member of the DAF-2/Insulin receptor-like signaling pathway which has roles in dauer formation, thermotolerance and adult longevity. Our lab has previously shown that VAB-1/EphR binds DAF-18. To further investigate the significance of this interaction as well as offer additional function to the proteins involved, I have shown that VAB-1/EphR is a negative regulator of DAF-18/PTEN at the protein level. Western blotting reveals that endogenous expression of DAF-18/PTEN is low in wild-type animals and expression is increased in a vab-1/ephR mutant. Additionally, VAB-1/EphR and DAF-18/PTEN are expressed in head neurons, oocytes and the germline precursor cells, Z2/Z3. vab-1/ephR mutants show increases longevity and sensitivity to dauer conditions which is consistent with increased DAF-18/PTEN activity. Lastly, daf-18(ok480) is able to suppress the oocyte maturation phenotype and increased MAPK expression displayed by vab-1(dx31) animals, providing genetic evidence of an interaction. By identifying the tissues where these proteins are co-expressed and substantiating the interaction with multiple analyses, novel roles may be proposed for each: VAB-1/EphR in DAF-2/Insulin signaling and DAF-18/PTEN in oocyte maturation downstream of VAB-1/EphR signaling. This work provides further understanding of how an organism coordinates complex developmental processes and reiterates the notion that cellular signaling is a complex network of interacting players. As many signaling pathways are evolutionarily conserved, my research in C. elegans may provide a mechanism on how Eph RTKs and PTEN are regulated in more complex organisms, including humans.en
dc.format.extent15394328 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.subjectDAF-18en
dc.subjectPTENen
dc.subjectC. elegansen
dc.subjectVAB-1en
dc.subjectEph RTKen
dc.subjectProtein Interactionen
dc.subjectTumour Suppressoren
dc.titleExploring the Functional Significance of the Caenorhabditis elegans VAB-1 Eph RTK and DAF-18/PTEN Tumour Suppressor Interactionen
dc.typethesisen
dc.description.restricted-thesisWe are currently in the process of submitting a manuscript for publication based on the results of this thesis. We would like to keep the thesis restricted until the manuscript has been formally accepted.en
dc.description.degreeM.Sc.en
dc.contributor.supervisorChin-Sang, Ian D.en
dc.contributor.departmentBiologyen
dc.degree.grantorQueen's University at Kingstonen


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