CALYCULIN-A AND OKADAIC ACID - INHIBITORS OF PROTEIN PHOSPHATASE-ACTIVITY
CALYCULIN-A AND OKADAIC ACID - INHIBITORS OF PROTEIN PHOSPHATASE-ACTIVITY
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DOI：
10.1016/0006-291x(89)92189-x
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发表时间：
1989-03-31
影响因子：
3.1
通讯作者：
HARTSHORNE, DJ
中科院分区：
文献类型：
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作者：
ISHIHARA, H;MARTIN, BL;HARTSHORNE, DJ
花盏花素A和冈田酸可引起平滑肌纤维收缩。冈田酸是一种磷酸酶活性的抑制剂，本研究的目的是确定Calyculin A是否也抑制磷酸酶，并筛选这两种化合物对各种磷酸酶的影响，以及这两种化合物对各种磷酸酶的影响。化合物既不抑制酸性或碱性磷酸酶，也不抑制磷酸酪氨酸蛋白磷酸酶。这两个化合物都是2A型磷酸酶催化亚单位的有效抑制剂，IC50值在0.5~1 nM之间。对于蛋白磷酸酶的催化亚基-1，毛盏花素A是一种比冈田酸更有效的抑制剂，其IC50值约为2 nM，对冈田酸的IC50值在60~500 nM之间。两种化合物对肌球蛋白B的内源性磷酸酶均有抑制作用，其IC50值分别为0.3~0.7 nM和15~70 nM，对花蕾甲素和冈田酸的IC50分别为15~70 nM和0.3~0.7 nM。部分纯化的肌球蛋白B催化亚基对纤毛菌素A和冈田酸的IC50值分别为0.7和200 nm。因此，肌球蛋白B中磷酸酶的抑制模式与1型酶相似。
Calyculin A and okadaic acid induce contraction in smooth muscle fibers. Okadaic acid is an inhibitor of phosphatase activity and the aims of this study were to determine if calyculin A also inhibits phosphatase and to screen effects of both compounds on various phosphatases and to screen effects of both compounds on various phosphatases. Neither compound inhibited acid or alkaline phosphatases, nor the phosphotyrosine protein phosphatase. Both compounds were potent inhibitors of the catalytic subunit of type-2A phosphatase, with IC50 values of 0.5 to 1 nM. With the catalytic subunit of protein phosphatase type-1, calyculin A was a more effective inhibitor than okadaic acid, IC50 values for calyculin A for calyculin A were about 2 nM and for okadaic acid between 60 and 500 nM. The endogenous phosphatase of smooth muscle myosin B was inhibited by both compounds with IC50 values of 0.3 to 0.7 nM and 15 to 70 nM, for calyculin A and okadaic acid, respectively. The partially purified catalytic subunit from myosin B had IC50 values of 0.7 and 200 nM for calyculin A and okadaic acid, respectively. The pattern of inhibition for the phosphatase in myosin B therefore is similar to that of the type-1 enzyme.