Extracellular signal-regulated kinase phosphorylates tumor necrosis factor α-converting enzyme at threonine 735:: A potential role in regulated shedding
Extracellular signal-regulated kinase phosphorylates tumor necrosis factor α-converting enzyme at threonine 735:: A potential role in regulated shedding
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DOI：
10.1091/mbc.01-11-0561
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发表时间：
2002-06-01
影响因子：
3.3
通讯作者：
Pandiella, A
中科院分区：
文献类型：
--
作者：
Díaz-Rodríguez, E;Montero, JC;Pandiella, A
某些跨膜蛋白的外结构域可以通过细胞表面蛋白酶（称为分泌酶）的作用释放出来。在这里，我们研究了丝裂原活化蛋白激酶（MAPKs）如何控制膜蛋白的脱落。我们发现细胞外信号调节激酶（Erk）作为蛋白激酶c调节的TrkA切割的中间物。我们报道肿瘤坏死因子a转换酶（TACE）的胞浆尾部在苏氨酸735处被Erk磷酸化。此外，我们发现Erk和TACE有关联。Erk活化和苏氨酸735的存在有利于这种关联。与Erk途径相反，p38 MAPK能够在缺乏TACE活性的细胞中刺激TrkA的切割，这表明其他蛋白酶也参与了TrkA的脱落。这些结果表明，分泌酶能够区分引发膜蛋白外结构域分裂的不同刺激，并表明MAPKs的磷酸化可能调节膜分泌酶的蛋白水解功能。
The ectodomain of certain transmembrane proteins can be released by the action of cell surface proteases, termed secretases. Here we have investigated how mitogen-activated protein kinases (MAPKs) control the shedding of membrane proteins. We show that extracellular signal-regulated kinase (Erk) acts as an intermediate in protein kinase C-regulated TrkA cleavage. We report that the cytosolic tail of the tumor necrosis factor a-converting enzyme (TACE) is phosphorylated by Erk at threonine 735. In addition, we show that Erk and TACE associate. This association is favored by Erk activation and by the presence of threonine 735. In contrast to the Erk route, the p38 MAPK was able to stimulate TrkA cleavage in cells devoid of TACE activity, indicating that other proteases are also involved in TrkA shedding. These results demonstrate that secretases are able to discriminate between the different stimuli that trigger membrane protein ectodomain cleavage and indicate that phosphorylation by MAPKs may regulate the proteolytic function of membrane secretases.