The Nef protein of human immunodeficiency virus type 1 enhances serine phosphorylation of the viral matrix.
The human immunodeficiency virus type 1 matrix (MA) protein is phosphorylated during virion maturation on its C-terminal tyrosine and on several serine residues. Whereas MA tyrosine phosphorylation facilitates viral nuclear import, the significance of MA serine phosphorylation remains unclear. Here, we report that MA serine but not tyrosine phosphorylation is strongly enhanced by Nef. Mutations that abrogated the membrane association of Nef and its ability to bind a cellular serine/threonine kinase greatly diminished the extent of virion MA serine phosphorylation. Correspondingly, a protein kinase coimmunoprecipitated with Nef could phosphorylate MA on serine in vitro, producing a phosphopeptide pattern reminiscent of that of virion MA. Recombinant p21-activated kinase hPAK65, a recently proposed relative of the Nef-associated kinase, achieved a comparable result. Taken together, these data suggest that MA is a target of the Nef-associated serine kinase.
Swingler
S
S
Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Gallay
P
P
Camaur
D
D
Song
J
J
Abo
A
A
Trono
D
D
D015683:Gene Products, gag / Q000378:metabolism*; D015693:Gene Products, nef / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D009226:Myristates / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism*; D019000:Phosphotyrosine / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases; D014763:Viral Matrix Proteins / Q000378:metabolism*; D014771:Virion / Q000378:metabolism; D054311:nef Gene Products, Human Immunodeficiency Virus; D054462:p21-Activated Kinases
D015683:Gene Products, gag; D015693:Gene Products, nef; D009226:Myristates; D014763:Viral Matrix Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D010768:Phosphoserine; D019000:Phosphotyrosine; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D054462:p21-Activated Kinases