Selective redistribution of protein kinase C isozymes by thapsigargin and staurosporine.
Selective redistribution of protein kinase C isozymes by thapsigargin and staurosporine.
复制标题
毒胡萝卜素和十字孢菌素选择性重新分布蛋白激酶 C 同工酶。
DOI：
10.1093/carcin/13.11.1997
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发表时间：
1992
期刊：
影响因子：
4.7
通讯作者：
Jaken,S
中科院分区：
文献类型：
--
作者：
Kiley,SC;Parker,PJ;Fabbro,D;Jaken,S
蛋白激酶C（PKC）是佛波酯促肿瘤作用的主要细胞受体。佛波酯激活GH_4C_1大鼠垂体细胞中的α-、β-、δ-和α-PKC，并使其从可溶性重新分布为颗粒状。我们现在已经确定了几种非佛波酯肿瘤促进剂对PKC同工酶在GH4 C11细胞中分布的影响。不完全的肿瘤促进剂mezerein引起α-、β-、δ-和β-PKC的重新分布。因此，其不显示部分激动剂活性。磷酸酶抑制剂冈田酸没有引起任何同工酶的再分配。钙ATP酶抑制剂thapsigargin和ser/thr激酶抑制剂staurosporine引起β-PKC和δ-PKC的重新分布，在较小程度上。尽管对δ-和β-PKC的选择性作用机制尚不清楚，但这些数据清楚地表明，它们的亚细胞分布可通过不影响α-和β-PKC的途径进行调节。佛波酯激活的β-PKC与出现一个更缓慢迁移的免疫反应带的圆锥部分。在佛波酯处理期间，两种β-PKC形式都积累磷酸盐。磷酸化形式的β-PKC优先在颗粒级分中回收。虽然星形孢菌素引起再分布，它阻止了佛波醇二丁酸酯（PDBu）介导的双联体的上带的出现和两个带的磷酸化增加。尽管星形孢菌素能有效抑制PKC的催化活性，但星形孢菌素不能抑制PDBu-PKC介导的α-和β-PKC的再分布。因此，再分布不需要催化活性。
Protein kinase C (PKC) is the major cellular receptor for tumor promoting phorbol esters. Phorbol esters activate α-, β-, δ- and є-PKCs in GH4C1rat pituitary cells and cause their redistribution from a soluble to a particulate fraction. We have now characterized the effect of several non-phorbol ester tumor promoters on PKC isozyme distribution in GH4C1cells. The incomplete tumor promoter mezerein caused redistribution of α-, β-, δ- and є-PKCs. Thus, it did not display partial agonist activity. The phosphatase inhibitor okadaic acid did not cause redistribution of any isozyme. The calcium ATPase inhibitor thapsigargin and the ser/thr kinase inhibitor staurosporine caused redistribution of є-PKC and, to a lesser extent, δ-PKC. Although the mechanism of the selective effect on δ- and є-PKCs is not yet known, these data clearly demonstrate that their subcellular distribution can be regulated by a pathway that does not influence α- and β-PKCs. Phorbol ester activation of є-PKC was associated with appearance of a more slowly migrating immunoreactive band in the paniculate fraction. Both є-PKC forms accumulated phosphate during phorbol ester treatment The phosphorytated forms of є-PKC were preferentially recovered in the particulate fraction. Although staurosporine caused redistribution, it prevented the phorbol dibutyrate (PDBu)-mediated appearance of the upper band of the doublet and the increased phosphorylation of both bands. The PDBu-mediated redistribution of α- and β-PKCs was not inhibited by staurosporine, even though staurosporine effectively inhibited PKC catalytic activity. Therefore, catalytic activity is not required for redistribution.