GIT1 Phosphorylation on Serine 46 by PKD3 Regulates Paxillin Trafficking and Cellular Protrusive Activity*
| Autor: | Bettina Huck, Angelika Hausser, Ralf Kemkemer, Boris Macek, Mirita Franz-Wachtel, Monilola A. Olayioye |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
PTK2
Mutation Missense Cell Cycle Proteins macromolecular substances Biology Protein Serine-Threonine Kinases Biochemistry environment and public health Serine Focal adhesion Cell Movement Cell Line Tumor Humans Phosphorylation Protein kinase A Molecular Biology Paxillin Cytoskeleton Adaptor Proteins Signal Transducing Kinase Pyruvate Dehydrogenase Acetyl-Transferring Kinase Cell Biology Transport protein Cell biology carbohydrates (lipids) enzymes and coenzymes (carbohydrates) Protein Transport HEK293 Cells Amino Acid Substitution biology.protein health occupations |
| Zdroj: | The Journal of Biological Chemistry |
| Popis: | The continuous assembly and disassembly of focal adhesions is required for efficient cell spreading and migration. The G-protein-coupled receptor kinase-interacting protein 1 (GIT1) is a multidomain protein whose dynamic localization to sites of cytoskeletal remodeling is critically involved in the regulation of these processes. Here we provide evidence that the subcellular localization of GIT1 is regulated by protein kinase D3 (PKD3) through direct phosphorylation on serine 46. GIT1 phosphorylation on serine 46 was abrograted by PKD3 depletion, thereby identifying GIT1 as the first specific substrate for this kinase. A GIT1 S46D phosphomimetic mutant localized to motile, paxillin-positive cytoplasmic complexes, whereas the phosphorylation-deficient GIT1 S46A was enriched in focal adhesions. We propose that phosphorylation of GIT1 on serine 46 by PKD3 represents a molecular switch by which GIT1 localization, paxillin trafficking, and cellular protrusive activity are regulated. |
| Databáze: | OpenAIRE |
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