PMID- 10066731
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 11
DP  - 1999 Mar 12
TI  - Diacylglycerol kinase theta binds to and is negatively regulated by active RhoA.
PG  - 6820-2
AB  - 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.
FAU - Houssa, B
AU  - Houssa B
AD  - Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 
      121, 1066 CX Amsterdam, The Netherlands.
FAU - de Widt, J
AU  - de Widt J
FAU - Kranenburg, O
AU  - Kranenburg O
FAU - Moolenaar, W H
AU  - Moolenaar WH
FAU - van Blitterswijk, W J
AU  - van Blitterswijk WJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - EC 2.7.1.107 (Diacylglycerol Kinase)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - Catalysis
MH  - Cell Line
MH  - Diacylglycerol Kinase/*metabolism
MH  - GTP-Binding Proteins/*metabolism
MH  - Protein Binding
MH  - Subcellular Fractions/enzymology
EDAT- 1999/03/06 00:00
MHDA- 1999/03/06 00:01
CRDT- 1999/03/06 00:00
PHST- 1999/03/06 00:00 [pubmed]
PHST- 1999/03/06 00:01 [medline]
PHST- 1999/03/06 00:00 [entrez]
AID - 10.1074/jbc.274.11.6820 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Mar 12;274(11):6820-2. doi: 10.1074/jbc.274.11.6820.