THE V-KI-RAS ONCOGENE ALTERS CAMP NUCLEAR SIGNALING BY REGULATING THELOCATION AND THE EXPRESSION OF CAMP-DEPENDENT PROTEIN-KINASE II-BETA

Citation
A. Feliciello et al., THE V-KI-RAS ONCOGENE ALTERS CAMP NUCLEAR SIGNALING BY REGULATING THELOCATION AND THE EXPRESSION OF CAMP-DEPENDENT PROTEIN-KINASE II-BETA, The Journal of biological chemistry, 271(41), 1996, pp. 25350-25359
Citations number
59
Categorie Soggetti
Biology
ISSN journal
00219258
Volume
271
Issue
41
Year of publication
1996
Pages
25350 - 25359
Database
ISI
SICI code
0021-9258(1996)271:41<25350:TVOACN>2.0.ZU;2-0
Abstract
The v-Ki-Ras oncoprotein dedifferentiates thyroid cells and inhibits n uclear 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, RII beta, translocates from the membranes to the cytosol. RII beta mRNA and protein were eventually de pleted. These effects were mimicked by expressing AKAP45, a truncated version of the RII anchor protein, AKAP75. Because AKAP45 lacks membra ne targeting domains, it induces the translocation of PKAII to the cyt oplasm. Expression of AKAP45 markedly decreased thyroglobulin mRNA lev els and inhibited accumulation of C-PKA in the nucleus. Our results su ggest that: 1) The localization of PKAII influences cAMP signaling to the nucleus; 2) Ras alters the localization and the expression of PKAI I; 3) Translocation of PKAII to the cytoplasm reduces nuclear C-PKA ac cumulation, resulting in decreased expression of cAMP-dependent genes, including RII beta, TSH receptor, and thyroglobulin. The loss of RII beta permanently down-regulates thyroid-specific gene expression.