Activation of NFAT-dependent gene expression by Nef: conservation among divergent Nef alleles, dependence on SH3 binding and membrane association, and cooperation with protein kinase C-theta.
Here we show that the potential to regulate NFAT is a conserved property of different Nef alleles and that Nef residues involved in membrane targeting and SH3 binding are critical for this function. Cotransfection of an activated protein kinase C-theta (PKC-theta) with Nef implicated PKC-theta as a possible physiological cofactor of Nef in promoting NFAT-dependent gene expression and T-cell activation.
Manninen
A
A
Institute of Medical Technology, University of Tampere, FIN-33014 Tampere, Finland.
Huotari
P
P
Hiipakka
M
M
Renkema
G H
GH
Saksela
K
K
D000483:Alleles; D002462:Cell Membrane / Q000378:metabolism; D017124:Conserved Sequence / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015693:Gene Products, nef / Q000235:genetics / Q000378:metabolism*; D015754:Genes, nef; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D019169:Jurkat Cells; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011493:Protein Kinase C / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D054311:nef Gene Products, Human Immunodeficiency Virus; D018909:src Homology Domains / Q000502:physiology
D004268:DNA-Binding Proteins; D015693:Gene Products, nef; D007527:Isoenzymes; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D054311:nef Gene Products, Human Immunodeficiency Virus; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta