The role of calpain in the regulation of ADAM17-dependent GPIbα ectodomain shedding
The role of calpain in the regulation of ADAM17-dependent GPIbα ectodomain shedding
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DOI：
10.1016/j.abb.2010.01.003
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发表时间：
2010-03-15
影响因子：
3.9
通讯作者：
Dai, Kesheng
中科院分区：
文献类型：
--
作者：
Wang, Zhicheng;Shi, Quanwei;Dai, Kesheng
有证据表明，去整合素和金属蛋白酶17(ADAM17)和Calain都参与了对血小板膜糖蛋白(GP)Ibα胞外结构域的切割。然而，这两种酶在脱落过程中的关系尚不清楚。在这里，我们证明了钙离子载体A23187和α-凝血酶诱导的GPIBα脱落可被金属蛋白酶抑制剂GM6001完全抑制，而仅被Calain抑制剂部分抑制。钙蛋白酶激活剂地布卡因诱导的GPIBα脱落可被金属蛋白酶和钙蛋白酶抑制剂完全抑制。另一方面，Calain抑制剂并不能抑制由特异性激活ADAM17的试剂诱导的GPIBα脱落。此外，在表达野生型或突变型GPIB-IX的中国仓鼠卵巢细胞中，A23187诱导的GPIbα脱落也被Calain抑制剂部分抑制，而GM6001几乎完全抑制。因此，这些数据表明，Calain在调节依赖ADAM17的GPIbα在血小板和有核细胞中的胞外区脱落方面发挥了重要作用。(C)2010 Elsevier Inc.保留所有权利。
There are evidence that both a disintegrin and metalloproteinase 17 (ADAM17) and calpain are involved in platelet glycoprotein (GP)Ib alpha ectodomain cleavage. However, the relationship between the two enzymes in the shedding process remains unclear. Here we show that calcium ionophore A23187- and alpha-thrombin-induced GPIb alpha shedding is completely inhibited by the metalloproteinase inhibitor GM6001, whereas it is only partially inhibited by calpain inhibitors. Calpain activator dibucaine-induced GPIb alpha shedding was completely inhibited by both metalloproteinase and calpain inhibitors. On the other hand, calpain inhibitors did not inhibit GPIb alpha shedding induced by the reagents that specifically activate ADAM17. Furthermore, A23187-induced GPIb alpha shedding in Chinese hamster ovary cells expressing wildtype or mutant GPIb-IX was also partially inhibited by calpain inhibitors and almost completely inhibited by GM6001. Therefore, these data indicate that calpain plays an important role in the regulation of ADAM17-dependent GPIb alpha ectodomain shedding in both platelets and nucleated cells. (C) 2010 Elsevier Inc. All rights reserved.