RhoGTPases oscillate between an inactive GDP-bound state and an active GTP-bound state. The exchange of GDP for GTP is catalyzed by guanine nucleotide exchange factors (GEFs). Different modes of GEF activation allow for localized Rho signaling in response to specific stimuli. Lfc’s activity in normal cells is tightly regulated through phosphorylation, subcellular localization and protein-protein interactions. Having identified PKA and PP2A as the potential kinase and phosphatase regulating Lfc our work has concentrated on the importance of specific sites of phosphorylation on Lfc responsible for its regulation. We have confirmed T114 and S885 as the sites of phosphorylation mediating the mutually exclusive relationship of Lfc with 14-3-3 and Tctex1, both negative regulators of Lfc activity. We have also confirmed TIP41 as a member of the Lfc-PP2A complex. Future work will focus on determining if TIP41 mediates the Lfc-PP2A interaction and the signals involved in Lfc activation by dephosphorylation.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/18222 |
| Date | 05 January 2010 |
| Creators | Brunet, Andrea |
| Contributors | Rottapel, Robert |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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