Abstract
Receptor tyrosine kinase-mediated activation of the Raf-1 protein kinase is coupled to the small guanosine triphosphate (GTP)-binding protein Ras. By contrast, protein kinase C (PKC)-mediated activation of Raf-1 is thought to be Ras independent. Nevertheless, stimulation of PKC in COS cells led to activation of Ras and formation of Ras-Raf-1 complexes containing active Raf-1. Raf-1 mutations that prevent its association with Ras blocked activation of Raf-1 by PKC. However, the activation of Raf-1 by PKC was not blocked by dominant negative Ras, indicating that PKC activates Ras by a mechanism distinct from that initiated by activation of receptor tyrosine kinases.
MeSH terms
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Animals
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COS Cells
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Chlorocebus aethiops
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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Epidermal Growth Factor / pharmacology
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Guanosine Triphosphate / metabolism*
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Indoles / pharmacology
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Mutation
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism*
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Proto-Oncogene Proteins c-raf / genetics
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Proto-Oncogene Proteins c-raf / metabolism*
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Receptor, Muscarinic M1
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Receptors, Muscarinic / metabolism
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Signal Transduction
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Tetradecanoylphorbol Acetate / pharmacology
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ras Proteins / metabolism*
Substances
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CHRM1 protein, human
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Enzyme Inhibitors
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Indoles
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Receptor, Muscarinic M1
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Receptors, Muscarinic
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Epidermal Growth Factor
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Guanosine Triphosphate
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Proto-Oncogene Proteins c-raf
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Protein Kinase C
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Calcium-Calmodulin-Dependent Protein Kinases
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ras Proteins
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Tetradecanoylphorbol Acetate
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Ro 31-8220