Independent mechanisms of cyclic AMP and glucocorticoid action
Independent mechanisms of cyclic AMP and glucocorticoid action
复制标题
环磷酸腺苷和糖皮质激素作用的独立机制
作者：
U. Gehring;P. Coffino
在真核细胞中，环磷酸腺苷（cAMP）作为几种激素（例如，肾上腺素和某些多肽激素）的细胞内介质1，并在细胞增殖的调节中发挥重要作用2，3。已知这种环核苷酸通过激活蛋白激酶4，5发挥作用，蛋白激酶介导特定蛋白质的磷酸化，从而改变其生物活性。事实上，蛋白激酶的激活可能是环AMP在哺乳动物细胞中的唯一作用机制6，7。糖皮质激素和类固醇激素一般通过一种机制起作用，该机制涉及激素与特定细胞质受体蛋白的结合、受体-类固醇复合物易位到细胞核中以及与染色质的结合。在几个系统中，对糖皮质激素和环AMP的细胞反应非常相似，类固醇对环AMP介导过程的增强作用通常被称为“容许效应”（综述见参考文献10和11）。据报道，在几种细胞类型中，糖皮质激素可增加环AMP的细胞内浓度（尽管是适度的）（参考文献12-15）。这些观察结果表明，环核苷酸和糖皮质激素在其作用机制中可能有一些共同的远端步骤。我们已经测试了这一假设，克隆反应细胞的存在下，这两个效应和报告在这里，耐环AMP和糖皮质激素独立发生。
IN eukaryotic cells, cyclic adenosine monophosphate (cyclic AMP) acts as the intracellular mediator for several hormones (for example, adrenaline and certain polypeptide hormones)1 and plays an important part in the modulation of cell proliferation2,3. This cyclic nucleotide is known to function by activating a protein kinase4,5 which mediates the phosphorylation of specific proteins, thereby modifying their biological activity. The activation of protein kinase may, in fact, be the sole mechanism of action of cyclic AMP in mammalian cells6,7. Glucocorticoids, and steroid hormones in general, act through a mechanism8,9 which involves the binding of the hormone to specific cytoplasmic receptor proteins, the translocation of the receptor–steroid complex into the cell nucleus and the association with chromatin. The cellular responses to glucocorticoids and cyclic AMP are quite similar in several systems and the potentiating effect of the steroid on cyclic AMP-mediated processes is often referred to as ‘permissive effect’ (for reviews see refs 10 and 11). In several cell types glucocorticoids have been reported to increase, although moderately, the intracellular concentration of cyclic AMP (refs 12–15). These observations suggest that the cyclic nucleotide and glucocorticoids could have some distal step(s) in common in their mechanism of action. We have tested this hypothesis by cloning responsive cells in the presence of both effectors and report here that resistance to cyclic AMP and glucocorticoids occurs independently.