An inactivating point mutation demonstrates that interaction of cAMP response element binding protein (CREB) with the CREB binding protein is not sufficient for transcriptional activation.
The cAMP response element binding protein (CREB) mediates transcriptional activation in response to the cAMP signaling pathway. Several recent studies have suggested that phosphorylation-dependent interaction of CREB with a co-activator designated CREB binding protein (CBP) is a crucial step in mediating transcriptional responses to cAMP. In the present study we have determined that replacement of Ser142 of CREB with Asp greatly decreases the ability of the cAMP-dependent protein kinase to activate CREB. As Ser142 is located within the region of CREB that interacts with CBP, it seemed quite likely that mutations at this site might interfere with binding to CBP. However, both in vitro and in vivo protein-protein interaction assays revealed that replacement of Ser142 with Asp does not interfere with the binding of CREB to CBP. These studies argue strongly that although the binding of CREB to CBP is necessary, it is not sufficient for transcriptional responses to cAMP.
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Department of Cell Biology and Anatomy, Oregon Health Sciences University, Portland 97201, USA.
Maurer
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D000818:Animals; D001224:Aspartic Acid; D001665:Binding Sites; D050882:CREB-Binding Protein; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000378:metabolism*; D015870:Gene Expression; D007700:Kinetics; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000378:metabolism*; D016716:PC12 Cells; D010766:Phosphorylation; D017354:Point Mutation; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012694:Serine; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D017362:Cyclic AMP Response Element-Binding Protein; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D001224:Aspartic Acid; D012694:Serine; D000242:Cyclic AMP; D008156:Luciferases; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; C494365:Crebbp protein, rat; D017871:Calcium-Calmodulin-Dependent Protein Kinases