Choi E J, Wong S T, Dittman A H, Storm D R
Department of Pharmacology, University of Washington, Seattle 98195.
Biochemistry. 1993 Mar 2;32(8):1891-4. doi: 10.1021/bi00059a001.
Phorbol esters and activators of protein kinase C have been reported to either facilitate or inhibit increases in intracellular cAMP caused by activators of adenylyl cyclase. The variable responses to activators of protein kinase C may reflect, in part, the existence of distinct adenylyl cyclases present in animal cells. There are a family of adenylyl cyclases with different regulatory properties, and clones for six distinct types of adenylyl cyclase have been reported. Two of these enzymes, the type I and type III adenylyl cyclases, are stimulated by calcium and calmodulin whereas the others are not. In this study, we examined the effect of phorbol esters of the activity of the type I and type III adenylyl cyclases in whole cells. TPA markedly enhanced the forskolin responsiveness of the type I and type III adenylyl cyclases expressed in kidney 293 cells. The effect of TPA on the activity of the calmodulin-sensitive adenylyl cyclases was not mediated through increases in intracellular free calcium. These data suggest that activation of protein kinase C can elevate intracellular cAMP in animal cells that contain the type I or type III adenylyl cyclase.
据报道，佛波酯和蛋白激酶C激活剂可促进或抑制腺苷酸环化酶激活剂引起的细胞内cAMP增加。对蛋白激酶C激活剂的不同反应可能部分反映了动物细胞中存在不同的腺苷酸环化酶。存在一类具有不同调节特性的腺苷酸环化酶，并且已报道了六种不同类型腺苷酸环化酶的克隆。其中两种酶，即I型和III型腺苷酸环化酶，受钙和钙调蛋白刺激，而其他酶则不受刺激。在本研究中，我们研究了佛波酯对全细胞中I型和III型腺苷酸环化酶活性的影响。佛波酯醇显著增强了肾293细胞中表达的I型和III型腺苷酸环化酶对福斯高林的反应性。佛波酯醇对钙调蛋白敏感的腺苷酸环化酶活性的影响不是通过细胞内游离钙的增加介导的。这些数据表明，蛋白激酶C的激活可使含有I型或III型腺苷酸环化酶的动物细胞内的cAMP升高。
