Jans D A, Dierks-Ventling C, Hemmings B A
Friedrich Miescher-Institut, Basel, Switzerland.
Exp Cell Res. 1987 Sep;172(1):76-83. doi: 10.1016/0014-4827(87)90094-2.
Induction of urokinase-type plasminogen activator (uPA) in response to either reagents activating cAMP-dependent protein kinase (cAMP-PK) or the calcium ion phospholipid-dependent kinase (C-kinase) was compared in the LLC-PK1 and T47D cell lines. The two cell lines exhibited quantitatively different responses to calcitonin, to the phosphodiesterase inhibitor isobutylmethylxanthine, and to the adenylate cyclase activator forskolin. Both showed activation of cAMP-PK in response to all these reagents, with T47D cells displaying a greater extent of activation. T47D cells, however, failed to produce uPA in response to calcitonin, forskolin, or the cAMP analog 8-bromo-cAMP, whereas LLC-PK1 cells produced high levels of uPA in response to all these agents. Both cell lines responded to phorbol esters in terms of uPA induction, though to differing extents. Phorbol myristate acetate (PMA) was shown conclusively not to activate cAMP-PK in either cell line, even at concentrations 10-fold higher than those promoting maximal uPA induction. It was concluded that phorbol ester-mediated induction of uPA does not involve cAMP or cAMP-PK activation. These results are discussed in relation to proposed models concerning the role of cAMP-PK in uPA induction.
在LLC-PK1和T47D细胞系中，比较了尿激酶型纤溶酶原激活剂（uPA）对激活环磷酸腺苷依赖性蛋白激酶（cAMP-PK）的试剂或钙离子磷脂依赖性激酶（C激酶）的反应。这两种细胞系对降钙素、磷酸二酯酶抑制剂异丁基甲基黄嘌呤和腺苷酸环化酶激活剂福斯高林表现出数量上不同的反应。二者对所有这些试剂均表现出cAMP-PK的激活，其中T47D细胞的激活程度更大。然而，T47D细胞对降钙素、福斯高林或cAMP类似物8-溴-cAMP不产生uPA，而LLC-PK1细胞对所有这些试剂均产生高水平的uPA。两种细胞系对佛波酯的uPA诱导均有反应，只是程度不同。已明确表明，即使在浓度比促进最大uPA诱导的浓度高10倍的情况下，佛波醇肉豆蔻酸酯乙酸酯（PMA）在任一细胞系中均不激活cAMP-PK。得出的结论是，佛波酯介导的uPA诱导不涉及cAMP或cAMP-PK的激活。结合有关cAMP-PK在uPA诱导中作用的提出模型对这些结果进行了讨论。
