Protein kinase C isozymes and the regulation of diverse cell responses
Protein kinase C isozymes and the regulation of diverse cell responses
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DOI：
10.1152/ajplung.2000.279.3.l429
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发表时间：
2000-09-01
影响因子：
4.9
通讯作者：
Messing, RO
中科院分区：
文献类型：
--
作者：
Dempsey, EC;Newton, AC;Messing, RO
单个蛋白激酶C（PKC）同工酶与肺健康和疾病中重要的许多细胞反应有关，包括渗透性、收缩、迁移、肥大、增殖、凋亡和分泌。关于PKC活性调节机制的新观点，包括鉴定一种新的PKC激酶，3-磷酸肌醇依赖性激酶-1（PDK-1），其调节PKC的磷酸化，已经被提出。PKC和同工酶特异性结合蛋白（如活化的C-激酶和小窝蛋白的受体）的靶向易位的重要性已得到充分证实。磷酸化状态和定位现在被认为是同工酶活性和特异性的关键决定因素。个别PKC同工酶在增殖和凋亡中的作用的新概念正在出现。在相同的细胞系统中，所选择的同工酶的相反作用已经被定义。已经描述了与Wnt信号传导途径的偶联。PKC基因敲除小鼠的表型最近有报道。研究PKC同工酶及其在细胞反应中的作用的更具体的方法已经开发出来。不同的实验策略的优点和缺点进行了审查。确定了今后的调查方向。
Individual protein kinase C (PKC) isozymes have been implicated in many cellular responses important in lung health and disease, including permeability, contraction, migration, hypertrophy, proliferation, apoptosis, and secretion. New ideas on mechanisms that regulate PKC activity, including the identification of a novel PKC kinase, 3-phosphoinositide- dependent kinase-1 (PDK-1), that regulates phosphorylation of PKC, have been advanced. The importance of targeted translocation of PKC and isozyme-specific binding proteins (like receptors for activated C-kinase and caveolins) is well established. Phosphorylation state and localization are now thought to be key determinants of isozyme activity and specificity. New concepts on the role of individual PKC isozymes in proliferation and apoptosis are emerging. Opposing roles for selected isozymes in the same cell system have been defined. Coupling to the Wnt signaling pathway has been described. Phenotypes for PKC knockout mice have recently been reported. More specific approaches for studying PKC isozymes and their role in cell responses have been developed. Strengths and weaknesses of different experimental strategies are reviewed. Future directions for investigation are identified.