Transcription factor AP-2 activity is modulated by protein kinase A-mediated phosphorylation.
We recently reported that APOE promoter activity is stimulated by cAMP, this effect being mediated by factor AP-2 [Garcia et al. (1996) J. Neurosci. 16, 7550-7556]. Here, we study whether cAMP-induced phosphorylation modulates the activity of AP-2. Recombinant AP-2 was phosphorylated in vitro by protein kinase A (PKA) at Ser239. Mutation of Ser239 to Ala abolished in vitro phosphorylation of AP-2 by PKA, but not the DNA binding activity of AP-2. Cotransfection studies showed that PKA stimulated the effect of AP-2 on the APOE promoter, but not that of the S239A mutant. Therefore, cAMP may modulate AP-2 activity by PKA-induced phosphorylation of this factor.
Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de Madrid, Spain.
M A
MA
García
M
M
Campillos
A
A
Marina
F
F
Valdivieso
J
J
Vázquez
D019943:Amino Acid Substitution; D001057:Apolipoproteins E / Q000235:genetics; D001665:Binding Sites / Q000528:radiation effects; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D015345:Oligonucleotide Probes / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D017384:Sequence Deletion; D012694:Serine / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D001057:Apolipoproteins E; D004268:DNA-Binding Proteins; D015345:Oligonucleotide Probes; D009842:Oligopeptides; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D012694:Serine; C037642:kemptide; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases