Activation of Ste20 by Nef from human immunodeficiency virus induces cytoskeletal rearrangements and downstream effector functions in Saccharomyces cerevisiae

The negative factor (Nef) from human and simian immunodeficiency viruses is important for the pathogenesis of acquired immune deficiency syndrome. Amo ng other targets, it activates the Nef-associated kinase, which is related to the p21-activated kinase. In this study, we demonstrate that Nei activat es Ste20, the homolog of p21-activated kinase in Saccharomyces cerevisiae. Nei binds to the adaptor proteins semi and Ste20 via its proline-rich (PXXP ) and diarginine(RR) motifs, respectively. These interactions induce the mi togen-activated protein kinase and increase the rates of budding, sizes of cells, and patterns of mating projections. These effects of Nef depend on t he small GTPase Cdc42 and guanine nucleotide exchange factor Cdc24. Thus, s tudies in S. cerevisiae identified specific interactions between Nef and ce llular proteins and their associated signaling cascade. (C) 1999 Academic P ress.