Abstract
Cyclic adenosine monophosphate (cAMP) has tissue-specific effects on growth, differentiation, and gene expression. We show here that cAMP can activate the transcription factor Elk-1 and induce neuronal differentiation of PC12 cells via its activation of the MAP kinase cascade. These cell type-specific actions of cAMP require the expression of the serine/threonine kinase B-Raf and activation of the small G protein Rap1. Rap1, activated by mutation or by the cAMP-dependent protein kinase PKA, is a selective activator of B-Raf and an inhibitor of Raf-1. Therefore, in B-Raf-expressing cells, the activation of Rap1 provides a mechanism for tissue-specific regulation of cell growth and differentiation via MAP kinase.
MeSH terms
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Animals
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cattle
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Cell Differentiation / physiology
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Cell Membrane / enzymology
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Cyclic AMP / pharmacology*
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Cyclic AMP-Dependent Protein Kinases / metabolism
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DNA-Binding Proteins*
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Guanosine Triphosphate / metabolism
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Neurons / cytology
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Neurons / enzymology
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PC12 Cells / cytology
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PC12 Cells / drug effects
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PC12 Cells / enzymology
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Protein Serine-Threonine Kinases / metabolism*
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-raf
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Protozoan Proteins / metabolism*
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Rats
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Transcription Factors / metabolism
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ets-Domain Protein Elk-1
Substances
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DNA-Binding Proteins
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Elk1 protein, rat
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Proto-Oncogene Proteins
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Protozoan Proteins
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Transcription Factors
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ets-Domain Protein Elk-1
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rhoptry associated protein, Plasmodium
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Guanosine Triphosphate
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Cyclic AMP
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-raf
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Cyclic AMP-Dependent Protein Kinases
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Calcium-Calmodulin-Dependent Protein Kinases