Pawelek J M
J Cell Physiol. 1979 Mar;98(3):619-25. doi: 10.1002/jcp.1040980320.
Wild-type Cloudman S91 melanoma cells have a retarded rate of division when agents which raise cyclic AMP levels such as melanotropin, protaglandin E1, or cholera toxin are supplemented to the culture medium. A mutant cell line was isolated which had the opposite response, i.e., the mutant grew very slowly unless agents which raised cyclic AMP levels were present (Pawelek et al., '75a). In this report evidence is presented indicating that the molecular basis for the mutant phenotype resides in the major cyclic AMP-dependent protein kinase found in the cells. The mutant kinase had increased thermolability and an elevated activation constant for cyclic AMP over the corresponding wild-type kinase. It is proposed that the elevated requirement for cyclic AMP for the proliferation of cAdep cells is related to the elevated activation constant of the kinase, suggesting that the kinase is a positive regulator of proliferation in Cloudman S91 cells.
当向培养基中添加能提高环磷酸腺苷（cAMP）水平的物质，如促黑素、前列腺素E1或霍乱毒素时，野生型Cloudman S91黑色素瘤细胞的分裂速度会减慢。分离出了一种突变细胞系，其反应相反，即除非存在能提高cAMP水平的物质，否则该突变体生长非常缓慢（帕韦莱克等人，1975年a）。在本报告中，提供的证据表明突变体表型的分子基础在于细胞中发现的主要cAMP依赖性蛋白激酶。与相应的野生型激酶相比，突变型激酶的热稳定性增加，对cAMP的活化常数升高。有人提出，cAdep细胞增殖对cAMP的需求增加与激酶活化常数升高有关，这表明该激酶是Cloudman S91细胞增殖的正调节因子。
