Identification of the Nef-associated kinase as p21-activated kinase 2

Citation
Gh. Renkema et al., Identification of the Nef-associated kinase as p21-activated kinase 2, CURR BIOL, 9(23), 1999, pp. 1407-1410
Citations number
15
Categorie Soggetti
Experimental Biology
Journal title
CURRENT BIOLOGY
ISSN journal
09609822 → ACNP
Volume
9
Issue
23
Year of publication
1999
Pages
1407 - 1410
Database
ISI
SICI code
0960-9822(199912)9:23<1407:IOTNKA>2.0.ZU;2-5
Abstract
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.