Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Substitution
-
Apolipoproteins E / genetics
-
Binding Sites / radiation effects
-
Cyclic AMP / physiology
-
Cyclic AMP-Dependent Protein Kinases / genetics
-
Cyclic AMP-Dependent Protein Kinases / metabolism*
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / isolation & purification
-
DNA-Binding Proteins / metabolism*
-
Humans
-
Oligonucleotide Probes / metabolism
-
Oligopeptides / pharmacology
-
Peptide Fragments / chemical synthesis
-
Peptide Fragments / pharmacology
-
Phosphorylation / drug effects
-
Promoter Regions, Genetic / genetics
-
Recombinant Fusion Proteins / genetics
-
Recombinant Fusion Proteins / isolation & purification
-
Recombinant Fusion Proteins / metabolism
-
Sequence Deletion
-
Serine / genetics
-
Serine / metabolism
-
Serine / physiology
-
Transcription Factor AP-2
-
Transcription Factors / genetics
-
Transcription Factors / isolation & purification
-
Transcription Factors / metabolism*
-
Transcriptional Activation
-
Transfection
-
Tumor Cells, Cultured
-
Ultraviolet Rays
Substances
-
Apolipoproteins E
-
DNA-Binding Proteins
-
Oligonucleotide Probes
-
Oligopeptides
-
Peptide Fragments
-
Recombinant Fusion Proteins
-
Transcription Factor AP-2
-
Transcription Factors
-
Serine
-
kemptide
-
Cyclic AMP
-
Cyclic AMP-Dependent Protein Kinases