Biologically active lipids are regulators of Rac.GDI complexation.
Members of the Rho family of GTP-binding proteins are localized in the cytosol of cells by complexation with a protein known as (Rho)GDI. We show by sucrose gradient equilibrium sedimentation analysis that all of the Rac protein present in human neutrophil cytosol exists as a complex with (Rho)GDI under non-activating conditions. This interaction can be disrupted in the presence of various lipids which have been shown to have biological activity in a variety of systems, including NADPH oxidase activation. Particularly effective were arachidonic acid, phosphatidic acid, and phosphatidylinositols. These lipids were active at concentrations from 0.5-50 microM and were capable of disrupting complexation of (Rho)GDI with both GDP- and GTP-bound forms of Rac, although the latter were more sensitive to lipid. These data suggest that certain lipids generated in chemoattractant-stimulated neutrophils may play a role in modulating the activity of Rac and thus NADPH oxidase activity.
Chuang
T H
TH
Department of Immunology, Scripps Research Institute, La Jolla, California 92037.
Bohl
B P
BP
Bokoch
G M
GM
D002474:Cell-Free System; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020730:Guanine Nucleotide Dissociation Inhibitors; D006801:Humans; D066298:In Vitro Techniques; D007294:Inositol / Q000494:pharmacology; D008055:Lipids / Q000502:physiology*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010712:Phosphatidic Acids / Q000494:pharmacology; D010766:Phosphorylation; D020744:rac GTP-Binding Proteins; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
D020730:Guanine Nucleotide Dissociation Inhibitors; D008055:Lipids; D010712:Phosphatidic Acids; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D007294:Inositol; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins