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GENES & DEVELOPMENT 6:1621-1630, 1992
ISSN 0890-9369
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Research Papers

v-ras and protein kinase C dedifferentiate thyroid cells by down-regulating nuclear cAMP-dependent protein kinase A.

A Gallo, E Benusiglio, I M Bonapace, A Feliciello, S Cassano, C Garbi, A M Musti, M E Gottesman, and E V Avvedimento

Dipartimento di Biologia e Patologia Molecolare e Cellulare, Universita di Napoli, Italy.

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.



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