Gallo A, Feliciello A, Varrone A, Cerillo R, Gottesman M E, Avvedimento V E
Dipartimento di Biologia e Patologia Molecolare e Cellulare, II Facoltà di Medicina e Chirurgia, Università di Napoli Federico II, Italy.
Cell Growth Differ. 1995 Jan;6(1):91-5.
The expression of thyroglobulin and other thyroid-specific markers depends upon the activation of protein kinase A (PKA) by cyclic AMP. A rat thyroid cell line dedifferentiates when transformed with Ki-ras oncogene. The decrease in thyroglobulin gene expression parallels a reduction in the level of PKA nuclear catalytic subunit. We find that the activity of cAMP-responsive elements and thyroglobulin promoters is down-regulated in Ras-transformed cells. Transcription of a third cAMP-regulated gene, H-ferritin, is similarly reduced. cAMP-responsive element and H-ferritin expression were stimulated when intracellular cAMP levels were increased. Reactivation of the thyroglobulin promoter required depletion of PKC in addition to increased cAMP. We also find that v-Ras activation leads to a significant increase in membrane-bound PKC. These data support the idea that v-Ras via PKC inhibits the transmission of cAMP-PKA signals to the nucleus. We suggest that the thyroglobulin promoter is more sensitive than other cAMP-dependent promoters to reduced nuclear levels of PKA catalytic subunit.
甲状腺球蛋白及其他甲状腺特异性标志物的表达取决于环磷酸腺苷（cAMP）对蛋白激酶A（PKA）的激活作用。用Ki-ras癌基因转化大鼠甲状腺细胞系时，该细胞系会发生去分化。甲状腺球蛋白基因表达的降低与PKA核催化亚基水平的降低相一致。我们发现，在Ras转化的细胞中，cAMP反应元件和甲状腺球蛋白启动子的活性被下调。第三个cAMP调节基因H-铁蛋白的转录也同样减少。当细胞内cAMP水平升高时，cAMP反应元件和H-铁蛋白的表达受到刺激。甲状腺球蛋白启动子的重新激活除了需要增加cAMP外，还需要消耗蛋白激酶C（PKC）。我们还发现，v-Ras的激活导致膜结合型PKC显著增加。这些数据支持了这样一种观点，即v-Ras通过PKC抑制cAMP-PKA信号向细胞核的传递。我们认为，甲状腺球蛋白启动子比其他cAMP依赖性启动子对PKA催化亚基核水平的降低更敏感。
