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Title: | REGULATION OF RHOGAP DLC1 BY FAK, PP2A AND MEK/ERK IN CELL DYNAMICS | Authors: | ARCHNA RAVI | Keywords: | DLC1, regulation, cell dynamics | Issue Date: | 20-Aug-2013 | Citation: | ARCHNA RAVI (2013-08-20). REGULATION OF RHOGAP DLC1 BY FAK, PP2A AND MEK/ERK IN CELL DYNAMICS. ScholarBank@NUS Repository. | Abstract: | DLC1, a functional RhoGAP and tumor suppressor, affects the process of cell migration via its regulation of RhoA. A serine-rich multi-domain protein, DLC1 undergoes post-translational modifications such as phosphorylation. It has been identified as a downstream target for various kinases but effects of growth factors, which play a crucial role in the development and progression of cancer, on DLC1 have not yet been elucidated. We have identified a novel pathway involving the concerted action of Ras/Mek/Erk pathway, Focal adhesion kinase (FAK) and Protein phosphatase-2A (PP2A) to activate DLC1s GAP function. EGF stimulation not only leads to the phosphorylation of DLC1 but also that of FAK to inactivate it, thus allowing PP2A-mediated dephosphorylation at a secondary site on DLC1. This signalling cascade directly affects DLC1s effect on cell spreading and migration, which can be correlated to the reduced RhoA levels. | URI: | http://scholarbank.nus.edu.sg/handle/10635/48585 |
Appears in Collections: | Ph.D Theses (Open) |
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