Ca2+/calmodulin-dependent protein kinase II is required for microcystin-induced apoptosis
Ca2+/calmodulin-dependent protein kinase II is required for microcystin-induced apoptosis
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DOI：
10.1074/jbc.m109049200
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发表时间：
2002-01-25
影响因子：
4.8
通讯作者：
Doskeland, SO
中科院分区：
文献类型：
--
作者：
Fladmark, KE;Brustugun, OT;Doskeland, SO
有效的天然毒素微囊藻毒素、节球藻毒素和冈田酸能迅速诱导细胞死亡。在这里，我们表明，细胞凋亡与蛋白磷酸化事件，并可以阻止针对多功能钙/钙调蛋白依赖性蛋白激酶11（CaMKII）的蛋白激酶抑制剂。所用的抑制剂包括一组细胞渗透性蛋白激酶拮抗剂和CaMKII-定向肽抑制剂，通过显微注射或强制表达引入。此外，细胞凋亡可以诱导的活性形式的CaMKII的强制表达，但不与非活性CaMKII。它的结论是，致突变毒素，大概是通过其已知的能力，抑制丝氨酸/苏氨酸蛋白磷酸酶，可以导致CaMKII依赖的磷酸化事件，导致细胞死亡。
The potent natural toxins microcystin, nodularin, and okadaic acid act rapidly to induce apoptotie cell death. Here we show that the apoptosis correlates with protein phosphorylation events and can be blocked by protein kinase inhibitors directed against the multifunctional Ca2+/calmodulin-dependent protein kinase 11 (CaMKII). The inhibitors used comprised a battery of cell-permeable protein kinase antagonists and CaMKII-directed peptide inhibitors introduced by microinjection or enforced expression. Furthermore, apoptosis could be induced by enforced expression of active forms of CaMKII but not with inactive CaMKII. It is concluded that the apoptogenic toxins, presumably through their known ability to inhibit serine/threonine protein phosphatases, can cause CaMKII-dependent phosphorylation events leading to cell death.