THE N-TERMINUS OF NEF FROM HIV-1 SIV ASSOCIATES WITH A PROTEIN COMPLEX CONTAINING LCK AND A SERINE KINASE/

The Nef protein of human and primate lentiviruses is a key factor in H IV/SIV pathogenesis. Here we report that Nef associates with two diffe rent kinases, forming a multiprotein complex at the far N-terminus of the viral protein. One of the kinases was identified as Lck, whereas t he second protein was found to be a serine kinase that phosphorylated Nef and Lck in vitro and could be discriminated from the serine kinase identified previously. The Nef-associated kinase complex (NAKC) was d emonstrated in COS cells, in HIV-infected cells, and in vitro using re combinant Lck and Nef proteins. Deletion of a short amphipathic alpha- helix in the N-terminus, which was found to be conserved in all Nef pr oteins, inhibited association of the NAKC and significantly reduced vi rion infectivity.