p21-activated kinase 1 phosphorylates and regulates 14-3-3 binding to GEF-H1, a microtubule-localized Rho exchange factor
Autor: | Gary M. Bokoch, Benjamin P. Bohl, Charles C. King, Mira Krendel, Céline DerMardirossian, Frank Zenke |
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Rok vydání: | 2004 |
Předmět: |
animal structures
Tyrosine 3-Monooxygenase CDC42 GTPase Protein Serine-Threonine Kinases Transfection environment and public health Biochemistry Microtubules Jurkat Cells PAK1 Protein Interaction Mapping Animals Guanine Nucleotide Exchange Factors Humans Binding site Phosphorylation Molecular Biology Binding Sites Chemistry Cell Biology Cell biology enzymes and coenzymes (carbohydrates) Protein Transport 14-3-3 Proteins p21-Activated Kinases Microtubule Proteins Guanine nucleotide exchange factor biological phenomena cell phenomena and immunity Signal transduction Rho Guanine Nucleotide Exchange Factors Proto-oncogene tyrosine-protein kinase Src HeLa Cells |
Zdroj: | The Journal of biological chemistry. 279(18) |
ISSN: | 0021-9258 |
Popis: | GEF-H1 is a guanine nucleotide exchange factor for Rho whose activity is regulated through a cycle of microtubule binding and release. Here we identify a region in the carboxyl terminus of GEF-H1 that is important for suppression of its guanine nucleotide exchange activity by microtubules. This portion of the protein includes a coiled-coil motif, a proline-rich motif that may interact with Src homology 3 domain-containing proteins, and a potential binding site for 14-3-3 proteins. We identify GEF-H1 as a binding target and substrate for p21-activated kinase 1 (PAK1), an effector of Rac and Cdc42 GTPases, using an affinity-based screen and localize a PAK1 phosphorylation site to the inhibitory carboxyl-terminal region of GEF-H1. We show that phosphorylation of GEF-H1 at Ser(885) by PAK1 induces 14-3-3 binding to the exchange factor and relocation of 14-3-3 to microtubules. Phosphorylation of GEF-H1 by PAK may be involved in regulation of GEF-H1 activity and may serve to coordinate Rho-, Rac-, and Cdc42-mediated signaling pathways. |
Databáze: | OpenAIRE |
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