Abstract
A mechanism by which calcium-induced signals are transduced to the nucleus to activate transcription of the c-fos proto-oncogene has been characterized. The serum response element (SRE), a region of the c-fos gene which controls growth factor-induced transcription, is now shown to mediate c-fos transcription in response to activation of L-type voltage-sensitive calcium channels. Calcium-dependent transcriptional activation through the SRE is mediated by the serum response factor (SRF). Membrane depolarization induces phosphorylation of SRF at Ser-103, an event shown to enhance the ability of SRF to bind the SRE. Ca(2+)-induced SRF phosphorylation occurs via a pathway that may involve Ca2+/calmodulin-dependent kinases.
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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Base Sequence
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Calcium / metabolism
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Calcium Channels / physiology*
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Calcium-Calmodulin-Dependent Protein Kinase Type 4
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cell Membrane / physiology
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DNA Mutational Analysis
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Fungal Proteins / genetics
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Fungal Proteins / metabolism
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Gene Expression Regulation*
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Membrane Potentials
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Molecular Sequence Data
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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PC12 Cells
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Phosphorylation
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Promoter Regions, Genetic / genetics
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Proto-Oncogene Proteins c-fos / genetics*
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Rats
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Recombinant Fusion Proteins / metabolism
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Saccharomyces cerevisiae Proteins*
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Serum Response Factor
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Signal Transduction
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription, Genetic
Substances
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Calcium Channels
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DNA-Binding Proteins
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Fungal Proteins
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GAL4 protein, S cerevisiae
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Nuclear Proteins
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Proto-Oncogene Proteins c-fos
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Recombinant Fusion Proteins
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Saccharomyces cerevisiae Proteins
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Serum Response Factor
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Transcription Factors
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Calcium-Calmodulin-Dependent Protein Kinase Type 4
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Calcium-Calmodulin-Dependent Protein Kinases
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Camk4 protein, rat
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Calcium