title: GTPase activity of small GTP-binding proteins in HL-60 membranes is stimulated by arachidonic acid.
abstract: The GTPase activity of membranes isolated from differentiated HL-60 cells was investigated to obtain information about the possible involvement of membrane-bound GTP-binding proteins in the regulation of the NADPH oxidase. A more than tenfold increase in the rate of hydrolysis of membrane-bound GTP was observed when cytosol and arachidonic acid were added simultaneously, i.e. under the same conditions where NADPH oxidase becomes activated. There were parallel changes in GTPase and NADPH oxidase activities when the concentration of arachidonic acid or the species of the fatty acid was varied or different detergents were applied. Separation of the GTP-binding proteins of the solubilized membrane by sucrose density gradient centrifugation, allowed us to ascribe the observed effect to the stimulation of the GTPase activity of small GTP-binding proteins by cytosolic component(s). Indirect evidence suggests that, in contrast to the effect upon recombinant ras and ras-GTPase-activating protein, in intact HL-60 membranes the interaction of rap1A with rap-GTPase-activating protein, is strongly enhanced by arachidonic acid.
authors.affiliation: Department of Physiology, Semmelweis Medical University, Budapest, Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Ligeti
authors.forename: V
authors.initials: V
authors.lastname: Pizon
authors.forename: A
authors.initials: A
authors.lastname: Wittinghofer
authors.forename: P
authors.initials: P
authors.lastname: Gierschik
authors.forename: K H
authors.initials: KH
authors.lastname: Jakobs
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019255:NADPH Oxidases; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D011994:Recombinant Proteins; D016718:Arachidonic Acid; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins