251. The tumor suppressor protein DLC1 is regulated by PKD-mediated GAP domain phosphorylation
- Author
-
Stephan A. Eisler, Monilola A. Olayioye, Simone Schmid, Patrik Erlmann, Mamta Jaiswal, Angelika Hausser, Peter Hoffmann, Rolf-Peter Scholz, Mohammed Reza Ahmadian, Johan O. R. Gustafsson, Scholz, Rolf Peter, Gustafsson, Johan OR, Hoffmann, Peter, Jaiswal, Mamta, Ahmadian, Mohammad Reza, Eisler, Stephan A, Erlmann, Patrik, Schmid, Simone, Hausser, Angelika, and Olayioye, Monilola
- Subjects
tumor suppressor ,GTPase activating protein ,Mutant ,Down-Regulation ,Biology ,Mass Spectrometry ,serine phosphorylation ,law.invention ,Serine ,law ,Cell Line, Tumor ,Humans ,Protein Interaction Domains and Motifs ,Phosphorylation ,Protein Kinase C ,Binding Sites ,protein kinase D (PKD) ,Tumor Suppressor Proteins ,GTPase-Activating Proteins ,Cell Biology ,Autophagy-related protein 13 ,Molecular biology ,In vitro ,Merlin (protein) ,Gene Expression Regulation, Neoplastic ,Suppressor ,Female ,DLC1 ,rho signaling - Abstract
Deleted in liver cancer 1 (DLC1) is a tumor suppressor protein that is frequently down regulated in various tumor types. DLC1 contains a Rho GTPase activating protein (GAP) domain that appears tobe required for its tumor suppressive functions. Little is known about the molecular mechanisms that regulate DLC1. By mass spectrometry we have mapped a novel phosphorylation site within the DLC1 GAP domain on serine 807. Using a phospho-S807-specific antibody, our results identifyprotein kinase D (PKD) to phosphorylate this site in DLC1 in intact cells. Although phosphorylationon serine 807 did not directly impact on in vitro GAP activity, a DLC1 serine-to-alanine exchange mutant inhibited colony formation more potently than the wild type protein. Our results thus show that PKD-mediated phosphorylation of DLC1 on serine 807 negatively regulates DLC1 cellular function. Refereed/Peer-reviewed
- Published
- 2011