Tetraspanins Regulate ADAM10-Mediated Cleavage of TNF-α and Epidermal Growth Factor
Tetraspanins Regulate ADAM10-Mediated Cleavage of TNF-α and Epidermal Growth Factor
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DOI：
10.4049/jimmunol.181.10.7002
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发表时间：
2008-11-15
影响因子：
4.4
通讯作者：
Le Naour, Francoise
中科院分区：
文献类型：
--
作者：
Arduise, Cecile;Abache, Toufik;Le Naour, Francoise
几种细胞因子和生长因子通过解聚素和金属蛋白酶（ADAM）金属蛋白酶的作用，由膜锚定前体经蛋白水解裂解而释放。这些蛋白酶的活性通过很大程度上未知的机制受到调节。在本研究中，我们表明几种四跨膜蛋白（CD9、CD81、CD82）与抗体结合通过一种依赖于ADAM10的机制增加表皮生长因子和/或肿瘤坏死因子 -α的分泌。抗四跨膜蛋白单克隆抗体对肿瘤坏死因子 -α释放的作用迅速，不是通过细胞间信号传导介导的，并且依赖于完整的丝裂原活化蛋白激酶/细胞外信号调节激酶1/2（MEK/Erk1/2）通路。它还与ADAM10在含四跨膜蛋白的斑块中聚集有关。我们还表明，很大一部分ADAM10与几种四跨膜蛋白相关联，这表明ADAM10是“四跨膜蛋白网络”的一个组成部分。这些数据表明四跨膜蛋白调节ADAM10对几种底物的活性，并阐明了四跨膜蛋白对膜的区室化作用如何控制细胞表面蛋白（如外切蛋白酶）的功能。《免疫学杂志》，2008年，181卷：7002 - 7013页。
Several cytokines and growth factors are released by proteolytic cleavage of a membrane-anchored precursor, through the action of ADAM (a disintegrin and metalloprotease) metalloproteases. The activity of these proteases is regulated through largely unknown mechanisms. In this study we show that Ab engagement of several tetraspanins (CD9, CD81, CD82) increases epidermal growth factor and/or TNF-alpha secretion through a mechanism dependent on ADAM10. The effect of anti-tetraspanin mAb on TNF-alpha release is rapid, not relayed by intercellular signaling, and depends on an intact MEK/Erk1/2 pathway. It is also associated with a concentration of ADAM10 in tetraspanin-containing patches. We also show that a large fraction of ADAM10 associates with several tetraspanins, indicating that ADAMIO is a component of the "tetraspanin web." These data show that tetraspanins regulate the activity of ADAM10 toward several substrates, and illustrate how membrane compartmentalization by tetraspanins can control the function of cell surface proteins such as ectoproteases. The Journal of Immunology, 2008, 181: 7002-7013.