GIT1 Phosphorylation on Serine 46 by PKD3 Regulates Paxillin Trafficking and Cellular Protrusive Activity
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| Authors: | Bettina Huck Ralf Kemkemer Mirita Franz-Wachtel Boris Macek Angelika Hausser Monilola A Olayioye |
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| Institution: | From the ‡Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.;the §Department of New Materials and Biosystems, Max Planck Institute for Intelligent Systems, Heisenbergstrasse 3, Stuttgart, Germany, and ;the ¶Proteome Center Tuebingen, Interfaculty Institute for Cell Biology, University of Tuebingen, Auf der Morgenstelle 15, 72076 Tuebingen, Germany |
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| Abstract: | 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. |
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| Keywords: | Cell Migration Cell Signaling Mass Spectrometry (MS) Phosphorylation Protein Kinase D (PKD) G-protein-coupled Receptor Kinase-interacting Protein (GIT1) Focal Adhesion |
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