title: CREB transcriptional activity in neurons is regulated by multiple, calcium-specific phosphorylation events.
abstract: The transcription factor CREB mediates diverse responses in the nervous system. It is not known how CREB induces specific patterns of gene expression in response to different extracellular stimuli. We find that Ca(2+) influx into neurons induces CREB phosphorylation at Ser133 and two additional sites, Ser142 and Ser143. While CREB Ser133 phosphorylation is induced by many stimuli, phosphorylation at Ser142 and Ser143 is selectively activated by Ca(2+) influx. The triple phosphorylation of CREB is required for effective Ca(2+) stimulation of CREB-dependent transcription, but the phosphorylation of Ser142 and Ser143, in addition to Ser133, disrupts the interaction of CREB with its cofactor CBP. These results suggest that Ca(2+) influx triggers a specific program of gene expression in neurons by selectively regulating CREB phosphorylation.
authors.affiliation: Division of Neuroscience, Children's Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jon M
authors.initials: JM
authors.lastname: Kornhauser
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Cowan
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Shaywitz
authors.forename: Ricardo E
authors.initials: RE
authors.lastname: Dolmetsch
authors.forename: Eric C
authors.initials: EC
authors.lastname: Griffith
authors.forename: Linda S
authors.initials: LS
authors.lastname: Hu
authors.forename: Chia
authors.initials: C
authors.lastname: Haddad
authors.forename: Zhengui
authors.initials: Z
authors.lastname: Xia
authors.forename: Michael E
authors.initials: ME
authors.lastname: Greenberg
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D050882:CREB-Binding Protein; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D004594:Electrophysiology; D007150:Immunohistochemistry; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D050882:CREB-Binding Protein; D002118:Calcium