Phosphorylation of CBP mediates transcriptional activation by neural activity and CaM kinase IV
Open accessAbstract
Activity-regulated transcription has been implicated in adaptive plasticity in the CNS. In many instances, this plasticity depends upon the transcription factor CREB. Precisely how neuronal activity regulates CREB remains unclear. To address this issue, we examined the phosphorylation state of components of the CREB transcriptional pathway. We show that NMDA activates transcription of CREB-responsive genes in hippocampal neurons, with ERK responsible for persistent CREB phosphorylation and CaM kinase IV (CaMKIV) responsible for phosphorylating the CREB coactivator, CBP. Ser301 of CBP was identified as a major target of CaMKIV phosphorylation in vitro and in vivo. CaM kinase inhibitors attenuated phosphorylation at Ser301 and blocked CBP-dependent transcription. Additionally, mutation of Ser301 impaired NMDA- and CaMKIV-stimulated transcription. These findings demonstrate that activity-induced CaMKIV signaling contributes to CREB/CBP-dependent transcription by phosphorylating CBP at Ser301.
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- Authors
- Impey, S., Fong, A. L., Wang, Y., Cardinaux, J.-R., Fass, D. M., Obrietan, K., Wayman, G. A., Storm, D. R., Soderling, T. R., & Goodman, R. H.
- Affiliations
- Oregon Health & Science University (US)
- The Ohio State University (US)
- University of Washington (US)
- Corresponding author
- Impey, Soren
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2002-04
- Volume
- 34
- Issue
- 2
- Pages
- 235-244
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1988181440
- Cited by
- 335
- References
- 64
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 13 · 2023: 2 · 2022: 13 · 2021: 5 · 2020: 9 · 2019: 3 · 2018: 5 · 2017: 10 · 2016: 15 · 2015: 11 · 2014: 10 · 2013: 16 · 2012: 13
- FWCI
- 9.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- American Heart Association
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- CaMKIV, CREB, transcriptional activation, neuronal activity, NMDA receptor, ERK, hippocampal neurons, activity-dependent plasticity
- MeSH terms
- Amino Acid Sequence, Animals, Gene Expression Regulation, Neurons, Nuclear Proteins, Phosphorylation, Transcription, Genetic, Signal Transduction, Trans-Activators, Receptors, N-Methyl-D-Aspartate, N-Methylaspartate, Cyclic AMP Response Element-Binding Protein, Calcium-Calmodulin-Dependent Protein Kinases, Excitatory Amino Acid Agonists, COS Cells, Mitogen-Activated Protein Kinases, CREB-Binding Protein, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 4
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