Date of Award

2004

Publication Type

Master Thesis

Degree Name

M.Sc.

Department

Biological Sciences

Keywords

Biology, Molecular

Supervisor

Ali, Adnan

Rights

info:eu-repo/semantics/openAccess

Abstract

Cellular survival and homeostasis is achieved due to the complex network of proteins present within cells to regulate responses to external stimuli. The phosphatidylinositol-3'-OH kinase (PI3' K) and the Wnt/Wg pathways, incorporate many important effector molecules and regulatory proteins to govern such cellular events as survival, apoptosis, cell-cell communication and fate determination. Protein kinase B (PKB) and glycogen synthase kinase-3 (GSK-3)/Shaggy are the main effector molecules in the PI3'K and Wnt/Wg pathways respectively, and rely on interactions with numerous regulatory proteins for initial phosphorylation or dephosphorylation, and subsequent activation. Integrin linked kinase (ILK) has been shown to act upstream of both PKB and GSK-3/Shaggy in mammalian systems, and regulates them in a PI3'K dependent manner and has been postulated as a PI3'K dependent protein kinase-2 (PDK-2) molecule. Studies with Drosophila ILK (D ILK) further validate this idea. In the present study, it is shown that DILK is 59% similar to human ILK and is regulated in a PI3'K dependent manner in vivo. DILK is able to phosphorylate PKB in vitro and this occurs at serine-505 residue, the Drosophila homologue to mammalian serine-473, in vivo. DILK was also shown to phosphorylate Shaggy, the GSK-3 homologue, in vitro. In addition, it was illustrated that insulin and wortmannin, PI3' K specific activator and inhibitor respectively, affect various genes at the nuclear level. Using microarray technology, insulin and wortmannin were shown to regulate the expression of 1151 genes, of which two were chosen for further verification by RT-PCR. Dream was verified to be up-regulated by insulin and the functional significance of this effect still remains to be determined.Dept. of Biological Sciences. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis2004 .S74. Source: Masters Abstracts International, Volume: 43-03, page: 0788. Adviser: Adnan Ali. Thesis (M.Sc.)--University of Windsor (Canada), 2004.

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