Abstract
Ras proteins are membrane-associated transducers of eternal stimuli to unknown intracellular targets. The constitutively activated v-ras oncogene induces dedifferentiation in thyroid cells. v-Ras appears to act by stimulating protein kinase C (PKC), which inhibits the nuclear migration of the catalytic subunit of the cAMP-dependent protein kinase A (PKA). Nuclear tissue-specific and housekeeping trans-acting factors that are dependent on phosphorylation by PKA are thus inactivated. Exclusion of the PKA subunit from the nucleus could represent a general mechanism for the pleiotropic effects of Ras and PKC on cellular growth and differentiation.
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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Cell Differentiation / drug effects
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Cell Differentiation / genetics*
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Cell Line
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Cell Nucleus / enzymology
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Cyclic AMP / pharmacology
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Down-Regulation / drug effects
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Down-Regulation / genetics
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Fluorescent Antibody Technique
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Molecular Sequence Data
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Oncogene Protein p21(ras) / genetics*
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Oncogene Protein p21(ras) / pharmacology
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Protein Kinase C / metabolism*
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Protein Kinases / genetics*
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Protein Kinases / metabolism
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Rats
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Sphingosine / pharmacology
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Temperature
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Thyroid Gland / cytology*
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Thyroid Gland / enzymology
Substances
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Cyclic AMP
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Protein Kinases
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Protein Kinase C
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Oncogene Protein p21(ras)
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Sphingosine