v-ras and protein kinase C dedifferentiate thyroid cells by down-regulating nuclear cAMP-dependent protein kinase A.
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.
Gallo
A
A
Dipartimento di Biologia e Patologia Molecolare e Cellulare, Universita di Napoli, Italy.
Benusiglio
E
E
Bonapace
I M
IM
Feliciello
A
A
Cassano
S
S
Garbi
C
C
Musti
A M
AM
Gottesman
M E
ME
Avvedimento
E V
EV
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology; D000242:Cyclic AMP / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005455:Fluorescent Antibody Technique; D008969:Molecular Sequence Data; D015689:Oncogene Protein p21(ras) / Q000235:genetics* / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D013110:Sphingosine / Q000494:pharmacology; D013696:Temperature; D013961:Thyroid Gland / Q000166:cytology* / Q000201:enzymology
D000242:Cyclic AMP; D011494:Protein Kinases; D011493:Protein Kinase C; D015689:Oncogene Protein p21(ras); D013110:Sphingosine