Translocation of protein kinase C in human leukemia cells susceptible or resistant to differentiation induced by phorbol 12-myristate 13-acetate.
Translocation of protein kinase C in human leukemia cells susceptible or resistant to differentiation induced by phorbol 12-myristate 13-acetate.
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DOI：
10.1073/pnas.83.19.7316
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发表时间：
1986-10
影响因子：
11.1
通讯作者：
Y. Homma;C. Henning-Chubb;E. Huberman
中科院分区：
文献类型：
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作者：
Y. Homma;C. Henning-Chubb;E. Huberman
我们研究了细胞对佛波醇 12-肉豆蔻酸酯 13-乙酸酯 (PMA) 诱导的分化的敏感性与钙和磷脂依赖性蛋白激酶（蛋白激酶 C）活性从细胞质到细胞膜的亚细胞易位之间的可能关系。在许多人类白血病细胞系中分析了这两个事件，包括早幼粒细胞系 HL-60 的四种细胞变体，它们对 PMA 诱导的分化表现出不同程度的敏感性。分化细胞的表型特征在于与针对成熟特异性细胞表面抗原的单克隆抗体的反应性增加、非特异性酯酶活性增加以及细胞形态成熟的获得。对每种细胞类型中蛋白激酶 C 活性的亚细胞分布的分析表明，90% 的激酶活性存在于胞质部分，其余活性存在于膜部分。用 160 nM PMA 处理分化敏感细胞，处理后 5 分钟内，胞质部分中的蛋白激酶 C 活性降低了 60% 以上，而膜部分中的活性增加了 1500% 以上。在处理抗分化细胞后，没有发现蛋白激酶C活性的这种亚细胞重新分布。基于这些发现，我们认为蛋白激酶 C 活性的亚细胞易位过程（在 PMA 与该激酶结合后启动）是佛波二酯诱导细胞分化所必需的。
We investigated the possible relationship between the susceptibility of cells to differentiation induced by phorbol 12-myristate 13-acetate (PMA) and the subcellular translocation of calcium- and phospholipid-dependent protein kinase (protein kinase C) activity from the cytosol to the membrane. These two events were analyzed in a number of human leukemia cell lines, including four cell variants of the promyelocytic cell line HL-60 that exhibit different degrees of susceptibility to PMA-induced differentiation. The phenotype of the differentiated cells was characterized by increased reactivity with monoclonal antibodies against maturation-specific cell surface antigens, increased nonspecific esterase activity, and acquisition of morphological cell maturation. Analysis of the subcellular distribution of protein kinase C activity in each of these cell types revealed that 90% of the kinase activity was present in the cytosolic fraction, with the remaining activity in the membrane fraction. Treatment of the differentiation-susceptible cells with 160 nM PMA resulted, within 5 min after treatment, in a greater than 60% decrease in protein kinase C activity in the cytosolic fraction and a greater than 1500% increase in the activity in the membrane fraction. No such subcellular redistribution of protein kinase C activity was found after treatment of the differentiation-resistant cells. On the basis of these findings, we suggest that the process of subcellular translocation of protein kinase C activity, initiated after the binding of PMA to this kinase, is required for the induction of cell differentiation by this phorbol diester.