Inhibitory effect of arachidonic acid on GTPase activating protein is antagonized by 1-stearoyl, 2-arachidonoyl glycerol.
The intrinsic GTPase activity of cellular protein p21ras is strongly increased by cytosolic GTPase activating protein (GAP). The activity of this enzyme has been shown to be inhibited by arachidonic acid. We report here that this inhibition is antagonized by the presence of 1-stearoyl, 2-arachidonoyl glycerol. This effect is structure specific and dose dependent, being maximum at 200 micrograms/ml of diacylglycerol (DG). These results suggest that production of DG in response to hormones or growth factors stimulation could indirectly modulate the interaction between p21ras and GAP.
Homayoun
P
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Department of Molecular Biology, Cleveland Clinic Foundation, OH 44106.
Stacey
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DW
D000818:Animals; D000911:Antibodies, Monoclonal; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004075:Diglycerides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D020558:GTP Phosphohydrolases / Q000378:metabolism; D020690:GTPase-Activating Proteins; D006160:Guanosine Triphosphate / Q000378:metabolism; D007700:Kinetics; D011506:Proteins / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D011817:Rabbits / Q000276:immunology; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D020703:ras GTPase-Activating Proteins
D000911:Antibodies, Monoclonal; D004075:Diglycerides; D020690:GTPase-Activating Proteins; D011506:Proteins; D011994:Recombinant Proteins; D020703:ras GTPase-Activating Proteins; D016718:Arachidonic Acid; C075809:1-stearoyl-2-arachidonoylglycerol; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D016283:Proto-Oncogene Proteins p21(ras)