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Only in Ret\/PTC1-positive TPC-1 cells did cAMP markedly inhibit the Raf\/ERK cascade, leading to mTOR pathway inhibition, repression of cyclin D1 and p21 and p27 accumulation. p27 knockdown did not prevent the DNA synthesis inhibition. In the other cells, cAMP little affected these signaling cascades and levels of cyclins D or CDK inhibitors. However, cAMP differentially inhibited the pRb-kinase activity and T172-phosphorylation of CDK4 complexed to cyclin D1 or cyclin D3, whereas CDK-activating kinase activity remained unaffected. At variance with current conceptions, our studies in thyroid carcinoma cell lines and previously in normal thyrocytes identify the activating phosphorylation of CDK4 as a common target of opposite cell cycle regulations by cAMP, irrespective of its impact on classical mitogenic signaling cascades and expression of CDK4 regulatory partners.<\/jats:p>","DOI":"10.1091\/mbc.e08-06-0617","type":"journal-article","created":{"date-parts":[[2008,9,18]],"date-time":"2008-09-18T00:53:59Z","timestamp":1221699239000},"page":"4814-4825","source":"Crossref","is-referenced-by-count":44,"title":["Cyclic AMP Inhibits the Proliferation of Thyroid Carcinoma Cell Lines through Regulation of CDK4 Phosphorylation"],"prefix":"10.1091","volume":"19","author":[{"given":"Ana Sofia","family":"Rocha","sequence":"first","affiliation":[{"name":"*Institute of Interdisciplinary Research (IRIBHM), Universit\u00e9 Libre de Bruxelles, Campus Erasme, B-1070 Brussels, Belgium; and"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-465 Porto, Portugal"}]},{"given":"Sabine","family":"Paternot","sequence":"additional","affiliation":[{"name":"*Institute of Interdisciplinary Research (IRIBHM), Universit\u00e9 Libre de Bruxelles, Campus Erasme, B-1070 Brussels, Belgium; and"}]},{"given":"Katia","family":"Coulonval","sequence":"additional","affiliation":[{"name":"*Institute of Interdisciplinary Research (IRIBHM), Universit\u00e9 Libre de Bruxelles, Campus Erasme, B-1070 Brussels, Belgium; and"}]},{"given":"Jacques E.","family":"Dumont","sequence":"additional","affiliation":[{"name":"*Institute of Interdisciplinary Research (IRIBHM), Universit\u00e9 Libre de Bruxelles, Campus Erasme, B-1070 Brussels, Belgium; and"}]},{"given":"Paula","family":"Soares","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-465 Porto, Portugal"}]},{"given":"Pierre P.","family":"Roger","sequence":"additional","affiliation":[{"name":"*Institute of Interdisciplinary Research (IRIBHM), Universit\u00e9 Libre de Bruxelles, Campus Erasme, B-1070 Brussels, Belgium; and"}]}],"member":"1076","reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"8517","DOI":"10.1074\/jbc.M108867200","volume":"277","author":"Alt J. 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