Abstract
The cAMP response element-binding protein (CREB) is a plasticity-associated transcription factor that can potentially integrate cAMP and calcium signals at the gene activation level. We tested for convergent Ser-133 phosphorylation of CREB via dopamine D1/D5 receptors and L-type calcium channels in organotypic cultures of neonatal striatum. We found such convergence only transiently. Sustained CREB phosphorylation by D1/D5 receptor and L-type channel agonists was targeted to opposite (striosome and matrix) cellular phenotypes. Subsequent expression of the CRE-containing gene, c-fos, matched the divergent patterns of sustained CREB phosphorylation, and both divergent patterns could be switched by inhibition of phosphatases, including calcineurin. Control of the duration of CREB phosphorylation may be a critical regulator of CRE-mediated gene expression by dopamine and calcium.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Newborn / growth & development
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Animals, Newborn / metabolism
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Calcineurin
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Calcium Channels / physiology
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Calmodulin-Binding Proteins / physiology
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Corpus Striatum / cytology
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Corpus Striatum / growth & development*
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Corpus Striatum / metabolism*
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Cyclic AMP Response Element-Binding Protein / metabolism*
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Dopamine and cAMP-Regulated Phosphoprotein 32
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Electrophysiology
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Enzyme Inhibitors / metabolism
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Nerve Tissue Proteins / metabolism
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Neurons / metabolism
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Phosphoprotein Phosphatases / physiology
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Phosphoproteins*
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Phosphorylation
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Proto-Oncogene Proteins c-fos / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, Dopamine D1 / metabolism
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Time Factors
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Tissue Distribution
Substances
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Calcium Channels
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Calmodulin-Binding Proteins
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Cyclic AMP Response Element-Binding Protein
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Dopamine and cAMP-Regulated Phosphoprotein 32
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Enzyme Inhibitors
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Nerve Tissue Proteins
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Phosphoproteins
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Proto-Oncogene Proteins c-fos
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Receptors, Dopamine D1
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Calcineurin
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Phosphoprotein Phosphatases