Distinct serine residues in CBP and p300 are necessary for their activation by phenylephrine.
The ability of CREB binding protein (CBP) and p300 co-activators to stimulate transcription has previously been shown to be enhanced by treatment of cardiac cells with the hypertrophic agent phenylephrine (PE). This effect is dependent on activation of the mitogen activated protein kinase pathway (p42/44 MAPK). Here, we demonstrate the first identification of potential phosphorylation sites targeted by PE within the proteins CBP and p300. We show that serine 2015 of CBP and serine 89 of p300 are necessary for PE to stimulate the transcriptional activity of these proteins. Furthermore, we have shown that PE is capable of mediating phosphorylation of endogenous p300 at serine 89. This phosphorylation mediated regulation of CBP and p300 suggests a potential signal transduction pathway for the induction of cardiac cell hypertrophy by PE.
Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
Rosalind J
RJ
Gusterson
L Wuchao
LW
Yuan
David S
DS
Latchman
D000818:Animals; D050882:CREB-Binding Protein; D002478:Cells, Cultured; D050881:E1A-Associated p300 Protein; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D008156:Luciferases / Q000032:analysis; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D009687:Nuclear Proteins; D015534:Trans-Activators; D010656:Phenylephrine; D012694:Serine; D008156:Luciferases; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat; D050881:E1A-Associated p300 Protein; C494362:Ep300 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases