CREB: a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases.
The mechanism by which Ca2+ mediates gene induction in response to membrane depolarization was investigated. The adenosine 3',5'-monophosphate (cAMP) response element-binding protein (CREB) was shown to function as a Ca(2+)-regulated transcription factor and as a substrate for depolarization-activated Ca(2+)-calmodulin-dependent protein kinases (CaM kinases) I and II. CREB residue Ser133 was the major site of phosphorylation by the CaM kinases in vitro and of phosphorylation after membrane depolarization in vivo. Mutation of Ser133 impaired the ability of CREB to respond to Ca2+. These results suggest that CaM kinases may transduce electrical signals to the nucleus and that CREB functions to integrate Ca2+ and cAMP signals.
Sheng
M
M
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115.
Thompson
M A
MA
Greenberg
M E
ME
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D005656:Fungal Proteins / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005809:Genes, Regulator / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D010766:Phosphorylation; D011494:Protein Kinases / Q000494:pharmacology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D029701:Saccharomyces cerevisiae Proteins; D012694:Serine / Q000737:chemistry; D015398:Signal Transduction; D016385:TATA Box; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D012694:Serine; D000242:Cyclic AMP; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium