THE NEF PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENHANCES SERINE PHOSPHORYLATION OF THE VIRAL MATRIX

The human immunodeficiency virus type 1 matrix (MA) protein is phospho rylated during virion maturation on its C-terminal tyrosine and on sev eral serine residues. Whereas MA tyrosine phosphorylation facilitates viral nuclear import, the significance of MA serine phosphorylation re mains unclear. Here, we report that MA serine but not tyrosine phospho rylation is strongly enhanced by Nef. Mutations that abrogated the mem brane association of Nef and its ability to bind a cellular serine/thr eonine kinase greatly diminished the extent of virion MA serine phosph orylation. Correspondingly, a protein kinase coimmunoprecipitated with Nef could phosphorylate MA on serine in vitro, producing a phosphopep tide pattern reminiscent of that of virion MA. Recombinant p21-activat ed kinase hPAK65, a recently proposed relative of the Nef-associated k inase, achieved a comparable result. Taken together, these data sugges t that MA is a target of the Nef-associated serine kinase.