Diacylglycerol kinase theta binds to and is negatively regulated by active RhoA.

Article Details

Citation

Houssa B, de Widt J, Kranenburg O, Moolenaar WH, van Blitterswijk WJ

Diacylglycerol kinase theta binds to and is negatively regulated by active RhoA.

J Biol Chem. 1999 Mar 12;274(11):6820-2.

PubMed ID
10066731 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Transforming protein RhoAP61586Details
Diacylglycerol kinase thetaP52824Details