Mammalian EGF receptor activation by the rhomboid protease RHBDL2
Mammalian EGF receptor activation by the rhomboid protease RHBDL2
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DOI：
10.1038/embor.2011.50
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发表时间：
2011-05-01
期刊：
影响因子：
7.7
通讯作者：
Freeman, Matthew
中科院分区：
文献类型：
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作者：
Adrain, Colin;Strisovsky, Kvido;Freeman, Matthew
表皮生长因子受体（EGFR）在哺乳动物发育和疾病，特别是癌症中具有多种功能。大多数EGF配体是作为膜系前体合成的，它们的蛋白水解释放激活信号传导。在果蝇中，菱形膜内蛋白酶催化EGF家族配体的释放;然而，在哺乳动物中，这似乎主要由ADAM家族金属蛋白酶实现。我们在这里报告，EGF是一种有效的基板的哺乳动物菱形RHBDL 2。RHBDL 2在其跨膜结构域外切割EGF，从而促进其分泌并触发EGFR的活化。我们已经在几种肿瘤细胞系中鉴定了内源性RHBDL 2活性。
The epidermal growth factor receptor (EGFR) has several functions in mammalian development and disease, particularly cancer. Most EGF ligands are synthesized as membrane-tethered precursors, and their proteolytic release activates signalling. In Drosophila, rhomboid intramembrane proteases catalyse the release of EGF-family ligands; however, in mammals this seems to be primarily achieved by ADAM-family metalloproteases. We report here that EGF is an efficient substrate of the mammalian rhomboid RHBDL2. RHBDL2 cleaves EGF just outside its transmembrane domain, thereby facilitating its secretion and triggering activation of the EGFR. We have identified endogenous RHBDL2 activity in several tumour cell lines.