Protein kinase C in angiotensin II signalling in neonatal rat cardiac fibroblasts. Role in the mitogenic response.
Protein kinase C in angiotensin II signalling in neonatal rat cardiac fibroblasts. Role in the mitogenic response.
复制标题
新生大鼠心脏成纤维细胞血管紧张素 II 信号传导中的蛋白激酶 C。
DOI：
10.1111/j.1749-6632.1995.tb17419.x
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发表时间：
1995
影响因子：
5.2
通讯作者：
Baker,KM
中科院分区：
文献类型：
--
作者：
Booz,GW;Baker,KM
八肽激素血管紧张素 II (All) 对心脏细胞功能发挥多种作用，包括对收缩性、代谢、生长和基因表达的影响。 1 这些作用是通过 All 与质膜受体的结合来启动的，该受体刺激磷脂酶 Cß (PLC) 水解磷脂酰肌醇 4, 5-二磷酸，从而形成二酰甘油 (DAG) 和肌醇 1, 4, 5-三磷酸 (IP3)。随后细胞内 Ca2+ 的升高是由 IP3 介导的 Ca2+ 从细胞内储存中的释放引起的，与 DAG 一起激活蛋白激酶 C (PKC)，这是一个与其从细胞质到颗粒（包括质膜）区室的易位相关的过程。 2 在某些细胞类型中，Ca2+ 通道的延迟激活和/或（Ca2+ 或 PKC 引发的）PLC 或磷脂酶 D (PLD) 介导的磷脂酰胆碱水解持续形成 DAG 已被认为会导致 AH 持续激活 PKC。 3 由于激活 PKC 的佛波酯会引起许多与 All 相同的细胞反应，因此可以逻辑地预测 PKC 将在 AIL 启动的细胞内信号级联中发挥核心作用。支持这一结论的证据是间接的，并且有几个警告事项：与 DAG 相比，佛波酯代谢较差，因此会产生持久的、非生理性的 PKC 激活；老一类的 PKC 抑制剂对 PKC 的选择性较差；佛波酯是 PKC 的有效激活剂，导致一些底物选择性丧失，特别是在佛波酯超最大浓度下。 4 此外，迄今为止，已鉴定出形成三个主要组的 10 种 PKC 同工酶。 2 这些 PKC 同工酶的底物特异性不同
The octapeptide hormone, angiotensin II (All) exerts a number of actions on cardiac cellular function, including effects on contractility, metabolism, growth, and gene expression. 1 These actions are initiated by the binding of All to a plasma membrane receptor that stimulates phospholipase Cß (PLC) to hydrolyze phosphatidylinositol 4, 5-bisphosphate, thus forming diacylglycerol (DAG) and inositol 1, 4, 5-triphosphate (IP3). The subsequent rise in intracellular Ca2+ that results from IP3-mediated release of Ca2+ from intracellular stores, together with DAG, activates protein kinase C (PKC), a process associated with its translocation from the cytosolic to the particulate (including the plasma membrane) compartment of the cell. 2 In some cell types, a delayed activation of Ca2+ channels and/or sustained formation of DAG from (Ca2+-or PKC-initiated) PLC-or phospholipase D (PLD)-mediated hydrolysis of phosphatidylcholine has been proposed to result in persistent activation of PKC by AH. 3Since phorbol esters which activate PKC elicit many of the same cellular responses as All, it is logical to predict that PKC would play a central role in the intracellular signalling cascade initiated by AIL Evidence to support this conclusion, however, is circumstantial, and there are several cautionary notes: in contrast to DAG, phorbol esters are poorly metabolized and thusproduce a persistent, nonphysiological activation of PKC; the older class of PKC inhibitors are poorly selective for PKC; and phorbol esters are such potent activators of PKC, that some substrate selectivity is lost, particularly at supramaximal concentrations of phorbol esters. 4 Moreover, ten isozymes of PKC that form three major groups have been identified to date. 2 These PKC isozymes differ in substrate specificity