p21-activated kinase 1 plays a critical role in cellular activation by Nef.
The activation of Nef-associated kinase (NAK) by Nef from human and simian immunodeficiency viruses is critical for efficient viral replication and pathogenesis. This induction occurs via the guanine nucleotide exchange factor Vav and the small GTPases Rac1 and Cdc42. In this study, we identified NAK as p21-activated kinase 1 (PAK1). PAK1 bound to Nef in vitro and in vivo. Moreover, the induction of cytoskeletal rearrangements such as the formation of trichopodia, the activation of Jun N-terminal kinase, and the increase of viral production were blocked by an inhibitory peptide that targets the kinase activity of PAK1 (PAK1 83-149). These results identify NAK as PAK1 and emphasize the central role its kinase activity plays in cytoskeletal rearrangements and cellular signaling by Nef.
Fackler
O T
OT
Howard Hughes Medical Institute, Departments of Medicine, Microbiology, and Immunology, San Francisco, California 94143-0703, USA.
Lu
X
X
Frost
J A
JA
Geyer
M
M
Jiang
B
B
Luo
W
W
Abo
A
A
Alberts
A S
AS
Peterlin
B M
BM
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015693:Gene Products, nef / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D008164:Luminescent Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D014764:Viral Proteins / Q000096:biosynthesis; D054311:nef Gene Products, Human Immunodeficiency Virus; D054462:p21-Activated Kinases
D015693:Gene Products, nef; D008164:Luminescent Proteins; D010446:Peptide Fragments; D014764:Viral Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D049452:Green Fluorescent Proteins; C515903:PAK1 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases