Phorbol ester induces desensitization of adenylate cyclase and phosphorylation of the beta-adrenergic receptor in turkey erythrocytes.
Phorbol ester induces desensitization of adenylate cyclase and phosphorylation of the beta-adrenergic receptor in turkey erythrocytes.
复制标题
佛波酯诱导火鸡红细胞中腺苷酸环化酶的脱敏和 β-肾上腺素能受体的磷酸化。
DOI：
10.1073/pnas.81.14.4316
复制
发表时间：
1984
影响因子：
11.1
通讯作者：
Johnson,GL
中科院分区：
文献类型：
--
作者：
Kelleher,DJ;Pessin,JE;Ruoho,AE;Johnson,GL
火鸡红细胞与佛波酯佛波12-肉豆蔻酸酯13-乙酸酯（PMA）的孵育导致异丙肾上腺素刺激的腺苷酸环化酶活性的剂量和时间依赖性脱敏。与对照组相比，PMA处理的细胞膜具有异丙肾上腺素刺激的腺苷酸环化酶活性，降低了20%-40%，对毛喉素或氟化物激活腺苷酸环化酶的影响很小。PMA处理后，β-肾上腺素能受体数量没有变化，表明PMA的主要作用是解偶联受体与腺苷酸环化酶的刺激性鸟嘌呤核苷酸调节蛋白Ns的相互作用。在PMA存在或不存在下孵育的32 Pi标记的火鸡红细胞的β-肾上腺素能受体的纯化表明佛波酯能够诱导β-肾上腺素能受体磷酸化增加3倍。PMA的作用类似于火鸡红细胞中异丙肾上腺素和二丁酰cAMP诱导的腺苷酸环化酶脱敏过程中β-肾上腺素能受体的磷酸化。研究结果表明，减少受体-Ns耦合与受体磷酸化，佛波酯可以影响某些细胞类型的敏感性腺苷酸环化酶的反应。
Incubation of turkey erythrocytes with the phorbol ester phorbol 12-myristate 13-acetate (PMA) results in a dose- and time-dependent desensitization of isoproterenol-stimulated adenylate cyclase activity. Compared to controls, membranes from PMA-treated cells have an isoproterenol-stimulated adenylate cyclase activity that is decreased 20%-40%, with little effect on forskolin or fluoride activation of adenylate cyclase. No change in beta-adrenergic receptor number is observed after PMA treatment, indicating that the major effect of PMA is to uncouple receptor interactions with Ns, the stimulatory guanine nucleotide regulatory protein of adenylate cyclase. Purification of beta-adrenergic receptors from 32Pi-labeled turkey erythrocytes, incubated in the presence or absence of PMA, indicates that the phorbol ester is capable of inducing a 3-fold increase in phosphorylation of the beta-adrenergic receptor. The PMA effect is similar to the phosphorylation of the beta-adrenergic receptor during isoproterenol- and dibutyryl cAMP-induced desensitization of adenylate cyclase in turkey erythrocytes. The findings indicate that decreased receptor-Ns coupling is correlated with receptor phosphorylation and that phorbol esters can influence the responsiveness of hormone-sensitive adenylate cyclase in certain cell types.