Mammalian EGF receptor activation by the rhomboid protease RHBDL2 |
| |
Authors: | Adrain Colin Strisovsky Kvido Zettl Markus Hu Landian Lemberg Marius K Freeman Matthew |
| |
Institution: | 1MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK;2Molecular Genetics Lab, Institute of Health Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, 225 Chongqing Nan Road, Shanghai 200025, China;3ZMBH, DKFZ–ZMBH Allianz, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany |
| |
Abstract: | 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. |
| |
Keywords: | cancer EGF receptor intramembrane protease mammal rhomboid |
本文献已被 PubMed 等数据库收录! |
|