Glycogen synthase kinase-3 phosphorylates CdGAP at a consensus ERK 1 regulatory site
| Autor: | Nathalie Lamarche-Vane, Mayya Meriane, Eric I. Danek, Ibtissem Triki, Joseph Tcherkezian |
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| Rok vydání: | 2006 |
| Předmět: |
GTPase-activating protein
Proline Mitogen-Activated Protein Kinase 3 Molecular Sequence Data RAC1 macromolecular substances CDC42 Biology Biochemistry Cell Line Glycogen Synthase Kinase 3 Mice GSK-3 Cell Line Tumor Consensus Sequence Animals Humans Amino Acid Sequence Phosphorylation cdc42 GTP-Binding Protein Molecular Biology GSK3B Glycogen Synthase Kinase 3 beta GTPase-Activating Proteins Cell Biology Phosphoproteins Cell biology Cdc42 GTP-Binding Protein NIH 3T3 Cells Signal transduction |
| Zdroj: | The Journal of biological chemistry. 282(6) |
| ISSN: | 0021-9258 |
| Popis: | Rho GTPases regulate a multitude of cellular processes from cytoskeletal reorganization to gene transcription and are negatively regulated by GTPase-activating proteins (GAPs). Cdc42 GTPase-activating protein (CdGAP) is a ubiquitously expressed GAP for Rac1 and Cdc42. In this study, we set out to identify CdGAP-binding partners and, using a yeast two-hybrid approach, glycogen synthase kinase 3alpha (GSK-3alpha) was identified as a partner for CdGAP. GSK-3 exists in two isoforms, alpha and beta, and is involved in regulating many cellular functions from insulin response to tumorigenesis. We show that GSK-3alpha and -beta interact with CdGAP in mammalian cells. We also demonstrate that GSK-3 phosphorylates CdGAP both in vitro and in vivo on Thr-776, which we have previously shown to be an ERK 1/2 phosphorylation site involved in CdGAP regulation. We report that the mRNA and protein levels of CdGAP are increased upon serum stimulation and that GSK-3 activity is necessary for the up-regulation of the protein levels of CdGAP but not for the increase in mRNA. We conclude that GSK-3 is an important regulator of CdGAP and that regulation of CdGAP protein levels by serum presents a novel mechanism for cells to control Cdc42/Rac1 GTPase signaling pathways. |
| Databáze: | OpenAIRE |
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