Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters.
Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters.
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DOI：
10.1016/s0021-9258(18)34459-4
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发表时间：
1982-07
期刊：
影响因子：
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通讯作者：
M. Castagna;Y. Takai;K. Kaibuchi;K. Sano;U. Kikkawa;Y. Nishizuka
中科院分区：
文献类型：
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作者：
M. Castagna;Y. Takai;K. Kaibuchi;K. Sano;U. Kikkawa;Y. Nishizuka
促进肿瘤的佛波酯，如12-O-十四酰佛波醇-13-乙酸酯(TPA)，在体外直接激活钙激活的磷脂依赖的蛋白激酶(蛋白激酶C)，这通常需要不饱和的二酰甘油。动力学分析表明，TPA可以替代甘油二酯，大大提高了酶对钙离子和磷脂的亲和力。在生理条件下，这种酶的激活似乎与受体介导的磷脂酰肌醇的分解有关，这可能是由多种细胞外信使引起的，最终导致特定细胞功能的激活或增殖。以人血小板为模型系统，在完全没有磷脂酰肌醇分解的情况下，TPA被证明可以增强与释放反应相关的蛋白激酶C的特异性磷酸化。在体外系统中，已被证明具有促进肿瘤活性的各种佛波醇衍生物也能够激活这种蛋白激酶。
Tumor-promoting phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) directly activate in vitro Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C), which normally requires unsaturated diacylglycerol. Kinetic analysis indicates that TPA can substitute for diacylglycerol and greatly increases the affinity of the enzyme for Ca2+ as well as for phospholipid. Under physiological conditions, the activation of this enzyme appears to be linked to the receptor-mediated phosphatidylinositol breakdown which may be provoked by a wide variety of extracellular messengers, eventually leading to the activation of specific cellular functions or proliferation. Using human platelets as a model system, TPA is shown to enhance the protein kinase C-specific phosphorylation associated with the release reaction in the total absence of phosphatidylinositol breakdown. Various phorbol derivatives which have been shown to be active in tumor promotion are also capable of activating this protein kinase in in vitro systems.