The Nef protein of primate immunodeficiency viruses plays an important role
in the pathogenesis of acquired immunodeficiency syndrome (AIDS) [1,2]. Th
e interaction of Nef with the Nef-associated kinase (NAK) is one of the mos
t conserved properties of different human and simian immunodeficiency virus
(HIV and SIV) Nef alleles. The role of NAK association is currently not kn
own but it has been implicated in enhanced viral infectivity in cell cultur
e and in disease progression in SIV-infected macaques [3]. Previous studies
have indicated that NAK shares many features with the p21-activated kinase
s (PAKs) [3], but the molecular identity of NAK has remained unknown. We ha
ve generated specific antisera against PAKs 1-3, and expressed these kinase
s individually as epitope-tagged proteins. By using these reagents in exper
iments involving partial proteolytic mapping, and exploiting the unique abi
lity of PAK2 to serve as a caspase substrate, we have positively identified
NAK as PAK2. Interestingly, although ectopic PAK2 overexpression efficient
ly replaced endogenous PAK2 from the complex with Nef, the total Nef-associ
ated PAK2 activity was not increased, indicating the abundance of another c
ellular factor(s) as the limiting factor in Nef-PAK2 complex formation. Ide
ntification of NAK as PAK2 should now facilitate elucidation of its role as
a mediator of the pathogenic effects of Nef.