Characterization of microcystin-LR, a potent inhibitor of type 1 and type 2A protein phosphatases.
Characterization of microcystin-LR, a potent inhibitor of type 1 and type 2A protein phosphatases.
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DOI：
10.1016/s0021-9258(17)45384-1
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发表时间：
1990-11
期刊：
影响因子：
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通讯作者：
R. Honkanen;J. Zwiller;R. Moore;S. L. Daily;B. Khatra;M. Dukelow;A. Boynton
中科院分区：
文献类型：
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作者：
R. Honkanen;J. Zwiller;R. Moore;S. L. Daily;B. Khatra;M. Dukelow;A. Boynton
蛋白的磷酸化水平取决于蛋白激酶和蛋白磷酸酶的相对活性。然而，与蛋白激酶相比，关于丝氨酸/苏氨酸蛋白磷酸酶功能的研究要少得多。这在一定程度上是由于缺乏可用作探针的特定蛋白磷酸酶抑制剂。在本研究中，我们研究了微囊藻毒素-LR的抑制作用，这是一种与北半球发现的大多数铜绿微囊藻菌株相关的肝毒性环肽，被证明是1型(IC50=1.7 nM)和2A型(IC50=0.04 nM)蛋白磷酸酶的有效抑制因子。在相同条件下，微囊藻毒素-LR对1型和2A型磷酸酶的抑制作用是冈田酸的10倍以上。0.5 nM微囊藻毒素-LR可完全抑制哺乳动物细胞稀释液中的2A型蛋白磷酸酶，而1型蛋白磷酸酶在该浓度下仅有轻微的抑制作用。因此，微囊藻毒素-LR可能被证明是一个有用的探针，用于研究和鉴定由蛋白磷酸酶介导的细胞过程。
The level of protein phosphorylation is dependent on the relative activities of both protein kinases and protein phosphatases. By comparison with protein kinases, however, there have been considerably fewer studies on the functions of serine/threonine protein phosphatases. This is partly due to a lack of specific protein phosphatase inhibitors that can be used as probes. In the present study we characterize the inhibitory effects of microcystin-LR, a hepatotoxic cyclic peptide associated with most strains of the blue-green algae Microcystis aeruginosa found in the Northern hemisphere, that proves to be a potent inhibitor of type 1 (IC50 = 1.7 nM) and type 2A (IC50 = 0.04 nM) protein phosphatases. Microcystin-LR inhibited the activity of both type 1 and type 2A phosphatases greater than 10-fold more potently than okadaic acid under the same conditions. Type 2A protein phosphatases in dilute mammalian cell extracts were found to be completely inhibited by 0.5 nM microcystin-LR while type 1 protein phosphatases were only slightly affected at this concentration. Thus, microcystin-LR may prove to be a useful probe for the study and identification cellular processes which are mediated by protein phosphatases.