CREB transcriptional activity in neurons is regulated by multiple, calcium-specific phosphorylation events
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Kornhauser, JM
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机构:Harvard Univ, Sch Med, Div Neurosci, Childrens Hosp, Cambridge, MA 02138 USA
Kornhauser, JM
Cowan, CW
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机构:Harvard Univ, Sch Med, Div Neurosci, Childrens Hosp, Cambridge, MA 02138 USA
Cowan, CW
Shaywitz, AJ
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机构:Harvard Univ, Sch Med, Div Neurosci, Childrens Hosp, Cambridge, MA 02138 USA
Shaywitz, AJ
Dolmetsch, RE
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机构:Harvard Univ, Sch Med, Div Neurosci, Childrens Hosp, Cambridge, MA 02138 USA
Dolmetsch, RE
Griffith, EC
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机构:Harvard Univ, Sch Med, Div Neurosci, Childrens Hosp, Cambridge, MA 02138 USA
Griffith, EC
Hu, LS
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机构:Harvard Univ, Sch Med, Div Neurosci, Childrens Hosp, Cambridge, MA 02138 USA
Hu, LS
Haddad, C
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机构:Harvard Univ, Sch Med, Div Neurosci, Childrens Hosp, Cambridge, MA 02138 USA
Haddad, C
Xia, ZG
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机构:Harvard Univ, Sch Med, Div Neurosci, Childrens Hosp, Cambridge, MA 02138 USA
Xia, ZG
Greenberg, ME
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Harvard Univ, Sch Med, Div Neurosci, Childrens Hosp, Cambridge, MA 02138 USAHarvard Univ, Sch Med, Div Neurosci, Childrens Hosp, Cambridge, MA 02138 USA
Greenberg, ME
[1
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机构:
[1] Harvard Univ, Sch Med, Div Neurosci, Childrens Hosp, Cambridge, MA 02138 USA
[2] Harvard Univ, Sch Med, Dept Neurobiol, Cambridge, MA 02138 USA
[3] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA
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 Ca2+ 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 Ca2+ influx. The triple phosphorylation of CREB is required for effective Ca2+ 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 Ca2+ influx triggers a specific program of gene expression in neurons by selectively regulating CREB phosphorylation.