Diacylglycerol Kinase θ Binds to and Is Negatively Regulated by Active RhoA
| Autor: | Wouter H. Moolenaar, Brahim Houssa, John de Widt, Onno Kranenburg, Wim J. van Blitterswijk |
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| Rok vydání: | 1999 |
| Předmět: |
Diacylglycerol Kinase
COS cells RHOA Effector Cell Biology Plasma protein binding Phosphatidic acid Biology Biochemistry Molecular biology Catalysis Cell Line Cell biology chemistry.chemical_compound Diacylglycerol kinase theta chemistry GTP-Binding Proteins Second messenger system biology.protein Animals Molecular Biology Protein Binding Subcellular Fractions Diacylglycerol kinase |
| Zdroj: | Journal of Biological Chemistry. 274:6820-6822 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.274.11.6820 |
| Popis: | Diacylglycerol kinase (DGK) phosphorylates the second messenger diacylglycerol to yield phosphatidic acid. To date, very little is known about the regulation of DGK activity. We have previously identified the DGKtheta isotype, which is predominantly expressed in brain (Houssa, B., Schaap, D., van der Wal, J., Goto, K., Kondo, H., Yamakawa, A., Shibata, M., Takenawa, T., and Van Blitterswijk, W. J. (1997) J. Biol. Chem. 272, 10422-10428). We now report that DGKtheta binds specifically to activated RhoA in transfected COS cells as well as in nontransfected neuronal N1E-115 cells. Binding is abolished by a point mutation (Y34N) in the effector loop of RhoA. DGKtheta does not bind to inactive RhoA, nor to the other Rho-family GTPases, Rac or Cdc42. Like active RhoA, DGKtheta localizes to the plasma membrane. Strikingly, the binding of activated RhoA to DGKtheta completely inhibits DGK catalytic activity. Our results suggest that DGKtheta is a downstream effector of RhoA and that its activity is negatively regulated by RhoA. Through accumulation of newly produced diacylglycerol, RhoA-mediated inhibition of DGKtheta may lead to enhanced PKC activity in response to external stimuli. |
| Databáze: | OpenAIRE |
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