BRYOSTATIN, AN ACTIVATOR OF THE CALCIUM PHOSPHOLIPID-DEPENDENT PROTEIN-KINASE, BLOCKS PHORBOL ESTER-INDUCED DIFFERENTIATION OF HUMAN PROMYELOCYTIC LEUKEMIA-CELLS HL-60
BRYOSTATIN, AN ACTIVATOR OF THE CALCIUM PHOSPHOLIPID-DEPENDENT PROTEIN-KINASE, BLOCKS PHORBOL ESTER-INDUCED DIFFERENTIATION OF HUMAN PROMYELOCYTIC LEUKEMIA-CELLS HL-60
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DOI：
10.1073/pnas.83.5.1334
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发表时间：
1986-03-01
影响因子：
11.1
通讯作者：
BERKOW, RL
中科院分区：
文献类型：
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作者：
KRAFT, AS;SMITH, JB;BERKOW, RL
phobol酯结合并激活钙磷脂依赖性蛋白激酶（C激酶）。一些研究者认为C激酶的活化是诱导佛博尔酯生物效应的必要条件。我们的研究表明苔藓抑素，一种在人多形核白细胞中与磷酯受体结合的大环内酯，在人早幼粒细胞白血病细胞系HL-60中也与该受体结合。苔藓虫素可以在体外激活HL-60细胞中部分纯化的C激酶，当应用于体内HL-60细胞时，可以降低可测量的细胞质C激酶活性。与磷酯不同，苔藓抑素不能诱导HL-60细胞向巨噬细胞样分化；然而，苔藓抑素，以剂量依赖的方式，阻断phorbol酯诱导的HL-60细胞分化，如果在phorbol酯48小时内应用，则停止进一步分化。这些结果表明，某些药物对C激酶的激活不足以诱导HL-60细胞分化，并暗示佛波酯的一些生物学效应可能通过比以前认为的更复杂的机制发生。
Phorbol esters bind to and activate a calcium phospholipid-dependent protein kinase (C kinase). Some researchers believe that activation of C kinase is necessary for the induction of phorbol ester biologic effects. Our research indicates that bryostatin, a macrocyclic lactone that binds to the phorbol ester receptor in human polymorphonuclear leukocytes, also binds to this receptor in the human promyelocytic leukemia cell line, HL-60. Bryostatin activates partially purified C kinase from HL-60 cells in vitro, and when applied to HL-60 cells in vivo, it decreases measurable cytoplasmic C kinase activity. Unlike the phorbol esters, bryostatin is unable to induce a macrophage-like differentiation of HL-60 cells; however, bryostatin, in a dose-dependent fashion, blocks phorbol ester-induced differentiation of HL-60 cells and, if applied within 48 hr of phorbol esters, halts further differentiation. These results suggest that activation of the C kinase by some agents is not sufficient for induction of HL-60 cell differentiation and imply that some of the biologic effects of phorbol esters may occur through a more complex mechanism than previously thought.