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...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1989-01, Vol.243 (4890), p.522-526
Main Authors: Tsai, Men-Hwei, Yu, Chun-Li, Wei, Fu-Sheng, Stacey, Dennis W.
Format: Article
Language:English
Subjects:
Animals
Arachidonic Acid
Arachidonic Acids - pharmacology
Biochemistry
c-Ha-ras
c-Ha-ras protein
Cell regulation
Cellular control mechanisms
Diglycerides - pharmacology
Fatty acids
Glycerophospholipids
GTP Phosphohydrolases - metabolism
GTPase activating protein
GTPase-Activating Proteins
GTPases
Guanosine triphosphatase
Guanosine Triphosphate - metabolism
Lipid metabolism
Lipids
Liposomes
Mice
Mitogens
Nonesterified fatty acids
Phosphatidic acids
Phosphatidic Acids - pharmacology
Phosphatidylcholines
Phosphatidylinositols
Phosphatidylinositols - pharmacology
Phospholipids
Phospholipids - pharmacology
Physiological aspects
Protein metabolism
Proteins
Proteins - antagonists & inhibitors
Proteins - pharmacology
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins p21(ras)
ras GTPase-Activating Proteins
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Description
Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.2536192