TY - JOUR
T1 - The v-Ki-Ras oncogene alters cAMP nuclear signaling by regulating the location and the expression of cAMP-dependent protein kinase IIβ
AU - Feliciello, A.
AU - Giuliano, P.
AU - Porcellini, A.
AU - Garbi, C.
AU - Obici, S.
AU - Mele, E.
AU - Angotti, E.
AU - Grieco, D.
AU - Amabile, G.
AU - Cassano, S.
AU - Li, Y.
AU - Musti, Anna M.
AU - Rubin, Charles S.
AU - Gottesman, Max E.
AU - Avvedimento, Enrico V.
PY - 1996
Y1 - 1996
N2 - The v-Ki-Ras oncoprotein dedifferentiates thyroid cells and inhibits nuclear accumulation of the catalytic subunit of cAMP-dependent protein kinase. After activation of v-Ras or protein kinase C, the regulatory subunit of type II protein kinase A, RIIβ, translocates from the membranes to the cytosol. RIIβ mRNA and protein were eventually depleted. These effects were mimicked by expressing AKAP45, a truncated version of the RII anchor protein, AKAP75. Because AKAP45 lacks membrane targeting domains, it induces the translocation of PKAII to the cytoplasm. Expression of AKAP45 markedly decreased thyroglobulin mRNA levels and inhibited accumulation of C-PKA in the nucleus. Our results suggest that: 1) The localization of PKAII influences cAMP signaling to the nucleus; 2) Ras alters the localization and the expression of PKAII; 3) Translocation of PKAII to the cytoplasm reduces nuclear C-PKA accumulation, resulting in decreased expression of cAMP- dependent genes, including RIIβ, TSH receptor, and thyroglobulin. The loss of RIIβ permanently down-regulates thyroid-specific gene expression.
AB - The v-Ki-Ras oncoprotein dedifferentiates thyroid cells and inhibits nuclear accumulation of the catalytic subunit of cAMP-dependent protein kinase. After activation of v-Ras or protein kinase C, the regulatory subunit of type II protein kinase A, RIIβ, translocates from the membranes to the cytosol. RIIβ mRNA and protein were eventually depleted. These effects were mimicked by expressing AKAP45, a truncated version of the RII anchor protein, AKAP75. Because AKAP45 lacks membrane targeting domains, it induces the translocation of PKAII to the cytoplasm. Expression of AKAP45 markedly decreased thyroglobulin mRNA levels and inhibited accumulation of C-PKA in the nucleus. Our results suggest that: 1) The localization of PKAII influences cAMP signaling to the nucleus; 2) Ras alters the localization and the expression of PKAII; 3) Translocation of PKAII to the cytoplasm reduces nuclear C-PKA accumulation, resulting in decreased expression of cAMP- dependent genes, including RIIβ, TSH receptor, and thyroglobulin. The loss of RIIβ permanently down-regulates thyroid-specific gene expression.
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U2 - 10.1074/jbc.271.41.25350
DO - 10.1074/jbc.271.41.25350
M3 - Article
C2 - 8810300
AN - SCOPUS:10144233449
SN - 0021-9258
VL - 271
SP - 25350
EP - 25359
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 41
ER -