BIOLOGICALLY-ACTIVE LIPIDS ARE REGULATORS OF RAC-CENTER-DOT-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 com plex with (Rho)GDI under non-activating conditions. This interaction c an be disrupted in the presence of various lipids which have been show n to have biological activity in a variety of systems, including NADPH oxidase activation. Particularly effective were arachidonic acid, pho sphatidic acid, and phosphatidylinositols. These lipids were active at concentrations from 0.5-50 muM and were capable of disrupting complex ation of (Rho)GD1 with both GDP- and GTP-bound forms of Rac, although the latter were more sensitive to lipid. These data suggest that certa in lipids generated in chemoattractant-stimulated neutrophils may play a role in modulating the activity of Rac and thus NADPH oxidase activ ity.