The v-Ki-Ras oncogene alters cAMP nuclear signaling by regulating the location and the expression of cAMP-dependent protein kinase IIβ

A. Feliciello, P. Giuliano, A. Porcellini, C. Garbi, S. Obici, E. Mele, E. Angotti, D. Grieco, G. Amabile, S. Cassano, Y. Li, Anna M. Musti, Charles S. Rubin, Max E. Gottesman, Enrico V. Avvedimento

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)25350-25359
Number of pages10
JournalJournal of Biological Chemistry
Volume271
Issue number41
DOIs
StatePublished - 1996

Fingerprint

ras Genes
Thyroglobulin
Cyclic AMP-Dependent Protein Kinases
Cyclic AMP-Dependent Protein Kinase Type II
Thyroid Gland
Cytoplasm
Membranes
ras Proteins
Thyrotropin Receptors
Messenger RNA
Oncogene Proteins
Anchors
Gene expression
Cytosol
Protein Kinase C
Catalytic Domain
Proteins
Down-Regulation
Genes
Chemical activation

ASJC Scopus subject areas

  • Biochemistry

Cite this

The v-Ki-Ras oncogene alters cAMP nuclear signaling by regulating the location and the expression of cAMP-dependent protein kinase IIβ. / Feliciello, A.; Giuliano, P.; Porcellini, A.; Garbi, C.; Obici, S.; Mele, E.; Angotti, E.; Grieco, D.; Amabile, G.; Cassano, S.; Li, Y.; Musti, Anna M.; Rubin, Charles S.; Gottesman, Max E.; Avvedimento, Enrico V.

In: Journal of Biological Chemistry, Vol. 271, No. 41, 1996, p. 25350-25359.

Research output: Contribution to journalArticle

Feliciello, A, Giuliano, P, Porcellini, A, Garbi, C, Obici, S, Mele, E, Angotti, E, Grieco, D, Amabile, G, Cassano, S, Li, Y, Musti, AM, Rubin, CS, Gottesman, ME & Avvedimento, EV 1996, 'The v-Ki-Ras oncogene alters cAMP nuclear signaling by regulating the location and the expression of cAMP-dependent protein kinase IIβ', Journal of Biological Chemistry, vol. 271, no. 41, pp. 25350-25359. https://doi.org/10.1074/jbc.271.41.25350
Feliciello, A. ; Giuliano, P. ; Porcellini, A. ; Garbi, C. ; Obici, S. ; Mele, E. ; Angotti, E. ; Grieco, D. ; Amabile, G. ; Cassano, S. ; Li, Y. ; Musti, Anna M. ; Rubin, Charles S. ; Gottesman, Max E. ; Avvedimento, Enrico V. / The v-Ki-Ras oncogene alters cAMP nuclear signaling by regulating the location and the expression of cAMP-dependent protein kinase IIβ. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 41. pp. 25350-25359.
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AU - Garbi, C.

AU - Obici, S.

AU - Mele, E.

AU - Angotti, E.

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AU - Cassano, S.

AU - Li, Y.

AU - Musti, Anna M.

AU - Rubin, Charles S.

AU - Gottesman, Max E.

AU - Avvedimento, Enrico V.

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