Caspase cleavage of the MET receptor generates an HGF interfering fragment
Caspase cleavage of the MET receptor generates an HGF interfering fragment
复制标题
DOI：
10.1016/j.bbrc.2007.12.177
复制
发表时间：
2008-03-14
影响因子：
3.1
通讯作者：
Fafeur, Veronique
中科院分区：
文献类型：
--
作者：
Deheuninck, Julien;Foveau, Benedicte;Fafeur, Veronique
MET酪氨酸激酶受体由其配体HGF/SF激活，诱导几种细胞应答，包括存活。尽管如此，MET受体在应激条件下被其细胞内区域内的半胱天冬酶切割，产生具有促凋亡特性的40 kDa片段p40 MET。在这里，我们确定了这种切割使受体在质膜ESVD位点分裂，导致p100 MET的伴随产生，对应于MET受体的整个细胞外区域仍然跨越膜。该片段能够结合HGF/SF并阻止完整MET下游的HGF依赖性信号传导，证明其作为诱饵受体的功能。(C)2008年爱思唯尔公司All rights reserved.
The MET tyrosine kinase receptor activated by its ligand HGF/SF, induces several cellular responses, including survival. Nonetheless, the MET receptor is cleaved in stress conditions by caspases within its intracellular region, generating a 40 kDa fragment, p40 MET, with pro-apoptotic properties. Here, we established that this cleavage splits the receptor at the juxtamembrane ESVD site, causing the concomitant generation of p100 MET, corresponding to the entire extracellular region of the MET receptor still spanning the membrane. This fragment is able to bind HGF/SF and to prevent HGF-dependent signaling downstream of full MET, demonstrating its function as a decoy receptor. (C) 2008 Elsevier Inc. All rights reserved.