CREB Transcriptional Activity in Neurons Is Regulated by Multiple, Calcium-Specific Phosphorylation Events
Autor: | Adam J. Shaywitz, Eric C. Griffith, Christopher W. Cowan, Linda Hu, Jon M. Kornhauser, Chia A Haddad, Zhengui Xia, Michael E. Greenberg, Ricardo E. Dolmetsch |
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Rok vydání: | 2002 |
Předmět: |
inorganic chemicals
Transcription Genetic Neuroscience(all) macromolecular substances CREB environment and public health Phosphorylation cascade 03 medical and health sciences 0302 clinical medicine CREB in cognition Transcription (biology) Gene expression Amino Acid Sequence Phosphorylation CREB-binding protein Cyclic AMP Response Element-Binding Protein Transcription factor Cells Cultured 030304 developmental biology Neurons 0303 health sciences biology Chemistry General Neuroscience Nuclear Proteins CREB-Binding Protein Immunohistochemistry Molecular biology Electrophysiology enzymes and coenzymes (carbohydrates) Trans-Activators biology.protein bacteria Calcium 030217 neurology & neurosurgery |
Zdroj: | Neuron. 34:221-233 |
ISSN: | 0896-6273 |
DOI: | 10.1016/s0896-6273(02)00655-4 |
Popis: | 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. |
Databáze: | OpenAIRE |
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