Human immunodeficiency virus type 1 Nef associates with a member of the p21-activated kinase family.
Although human immunodeficiency virus (HIV) Nef is essential for the induction of AIDS, its biochemical function has remained an enigma. In this study, HIV Nef protein is shown to associate with a serine-threonine kinase that recognizes histone H4 as a substrate, is serologically related to rat p21-activated kinase (PAK), and is specifically activated by Rac and Cdc42. These characteristics define the Nef-associated kinase as belonging to the PAK family. PAKs initiate kinase cascades in response to environmental stimuli, and their identification as a target of Nef implicates these signaling molecules in HIV pathogenesis and provides a novel target for clinical intervention.
Nunn
M F
MF
Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
Marsh
J W
JW
D000163:Acquired Immunodeficiency Syndrome; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D020558:GTP Phosphohydrolases / Q000096:biosynthesis; D015693:Gene Products, nef / Q000302:isolation & purification / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism* / Q000472:pathogenicity; D006657:Histones / Q000378:metabolism; D006801:Humans; D016399:Lymphoma, T-Cell; D009842:Oligopeptides; D010455:Peptides / Q000302:isolation & purification / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013379:Substrate Specificity; D014162:Transfection; D014407:Tumor Cells, Cultured; D054311:nef Gene Products, Human Immunodeficiency Virus; D054462:p21-Activated Kinases
D015693:Gene Products, nef; D006657:Histones; D009842:Oligopeptides; D010455:Peptides; D011994:Recombinant Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D000255:Adenosine Triphosphate; C085706:FLAG peptide; C515907:PAK2 protein, human; C515910:Pak2 protein, rat; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D020558:GTP Phosphohydrolases