Tumor necrosis factor-α-converting enzyme is required for cleavage of erbB4/HER4
Tumor necrosis factor-α-converting enzyme is required for cleavage of erbB4/HER4
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DOI：
10.1074/jbc.275.14.10379
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发表时间：
2000-04-07
影响因子：
4.8
通讯作者：
Corfas, G
中科院分区：
文献类型：
--
作者：
Rio, C;Buxbaum, JD;Corfas, G
HER4是表皮生长因子受体家族的成员，在心脏和神经发育中具有重要的功能。HER4JM-a和JM-b两种HER4亚型的鉴定表明，HER4JM-a和JM-b在胞外膜旁区域和佛波酯刺激后对切割的敏感性不同，表明受体的胞外膜旁区域是蛋白质降解的关键。我们现在证明佛波醇酯和过钒酸盐是HER4 JM-a加工的有效刺激，并且HER4 JM-b亚型不会对任何所研究的刺激做出反应。我们还表明，在缺乏金属蛋白酶肿瘤坏死因子-α转换酶(TACE)的细胞中，HER4 JM-a不被切割，并且TACE在这些细胞中的重新表达恢复了HER4 JM-a的构成和调节过程。此外，我们还表明，HER4 JM-a膜旁区域的特异性序列足以使人对佛波醇12-肉豆蔻酸酯13-乙酸酯诱导的HERS受体切割具有敏感性。总之，我们提供的证据表明，TACE对于调节HER4JM-a受体的脱落是必不可少的。
HER4 is a member of the epidermal growth factor receptor family and has an essential function in heart and neural development. Identification of two HER4 isoforms, HER4 JM-a and JM-b, which differ in their extracellular juxtamembrane region and in their susceptibility to cleavage after phorbol ester stimulation, showed that the juxtamembrane region of the receptor is critical for proteolysis. We now demonstrate that phorbol ester and pervanadate are effective stimuli for HER4 JM-a processing and that the HER4 JM-b isoform does not undergo cleavage in response to any of the stimuli studied. We also show that HER4 JM-a is not cleaved in cells lacking the metalloprotease tumor necrosis factor-alpha-converting enzyme (TACE) and that reexpression of TACE in these cells restores constitutive and regulated processing of HER4 JM-a. Moreover, we show that the sequence specific to the HER4 JM-a juxtamembrane region is sufficient to confer susceptibility to phorbol 12-myristate 13-acetate-induced cleavage of the HERS receptor. In conclusion, we provide evidence that TACE is essential for the regulated shedding of the HER4 JM-a receptor.