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. Among other targets, it activates the Nef-associated kinase, which is related to the p21-activated kinase. In this study, we demonstrate that Nef activates Ste20, the homolog of p21-activated kinase in Saccharomyces cerevisiae. Nef binds to the adaptor proteins Bem1 and Ste20 via its proline-rich (PXXP) and diarginine (RR) motifs, respectively. These interactions induce the mitogen-activated protein kinase and increase the rates of budding, sizes of cells, and patterns of mating projections. These effects of Nef depend on the small GTPase Cdc42 and guanine nucleotide exchange factor Cdc24. Thus, studies in S. cerevisiae identified specific interactions between Nef and cellular proteins and their associated signaling cascade.
Plemenitas
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A
Institute of Biochemistry, Medical Faculty, Vrazov trg2, Ljubljana, 1000, Slovenia.
Lu
X
X
Geyer
M
M
Veranic
P
P
Simon
M N
MN
Peterlin
B M
BM
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000502:physiology*; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D015693:Gene Products, nef / Q000378:metabolism*; D006678:HIV / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010675:Pheromones; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae; D054311:nef Gene Products, Human Immunodeficiency Virus
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C490024:FUS1 protein, S cerevisiae; D005656:Fungal Proteins; D015693:Gene Products, nef; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010675:Pheromones; D029701:Saccharomyces cerevisiae Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; C073129:BEM1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D020930:MAP Kinase Kinase Kinases; C078754:STE20 protein, S cerevisiae; D019204:GTP-Binding Proteins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae