The effect of GTPase activating protein upon ras is inhibited by mitogenically responsive lipids.
Bacterially synthesized c-Ha-ras protein (Ras) was incubated with guanosine triphosphatase (GTPase) activating (GA) protein in the presence of various phospholipids. The stimulation of Ras GTPase activity by GA protein was inhibited in some cases. Among the lipids most active in blocking GA protein activity were lipids that show altered metabolism during mitogenic stimulation. These included phosphatidic acid (containing arachidonic acid), phosphatidylinositol phosphates, and arachidonic acid. Other lipids, including phosphatidic acid with long, saturated side chains, diacylglycerols, and many other common phospholipids, were unable to alter GA protein activity. The interaction of lipids with GA protein might be important in the regulation of Ras activity during mitogenic stimulation.
Tsai
M H
MH
Department of Molecular Biology, Cleveland Clinic Foundation, OH 44106.
Yu
C L
CL
Wei
F S
FS
Stacey
D W
DW
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D020690:GTPase-Activating Proteins; D006160:Guanosine Triphosphate / Q000378:metabolism; D008081:Liposomes; D051379:Mice; D008934:Mitogens; D010712:Phosphatidic Acids / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000494:pharmacology; D010743:Phospholipids / Q000494:pharmacology*; D011506:Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras); D020703:ras GTPase-Activating Proteins
D001095:Arachidonic Acids; D004075:Diglycerides; D020690:GTPase-Activating Proteins; D008081:Liposomes; D008934:Mitogens; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D010743:Phospholipids; D011506:Proteins; D011518:Proto-Oncogene Proteins; D020703:ras GTPase-Activating Proteins; D016718:Arachidonic Acid; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D016283:Proto-Oncogene Proteins p21(ras)