Phosphorylation of CBP mediates transcriptional activation by neural activity and CaM kinase IV

Soren Impey, Amy L. Fong, Yanhong Wang, Jean Rene Cardinaux, Daniel M. Fass, Karl Obrietan, Gary A. Wayman, Daniel R. Storm, Thomas R. Soderling, Richard H. Goodman

Research output: Contribution to journalArticle

271 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)235-244
Number of pages10
JournalNeuron
Volume34
Issue number2
DOIs
StatePublished - Apr 11 2002

ASJC Scopus subject areas

  • Neuroscience(all)

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    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. (2002). Phosphorylation of CBP mediates transcriptional activation by neural activity and CaM kinase IV. Neuron, 34(2), 235-244. https://doi.org/10.1016/S0896-6273(02)00654-2