THE HIV-1 NEF PROTEIN INTERFERES WITH PHOSPHATIDYLINOSITOL 3-KINASE ACTIVATION-1

nef is a human immunodeficiency virus (HIV) gene encoding a 27-kDa myr istoylated protein with structural features of a signal transducing mo lecule, but whose functions are largely unknown. We studied the intera ctions of Nef with the signal transduction pathways triggered by the p latelet-derived growth factor (PDGF) receptor. The association of phos phatidylinositol (PI) S-kinase with the activated receptor was severel y impaired by nef expression. Conversely, PDGF-induced receptor tyrosi ne phosphorylation, binding to phospholipase C-gamma and to Res-GAP we re not modified. Microtubule-associated protein kinase activation and intracellular calcium influx in response to PDGF were either unaffecte d or only slightly enhanced. Nef significantly reduced the proliferati ve response to the growth factor, white the chemotactic response was u nchanged. These data show that Nef affects selectively the PI 3-kinase signaling pathway and suggest that this interference results in some of the HIV adverse effects on host cell functions.