Mammalian EGF receptor activation by the rhomboid protease RHBDL2

Colin Adrain; Kvido Strisovsky; Markus Zettl; Landian Hu; Marius K Lemberg; Matthew Freeman

doi:10.1038/embor.2011.50

journal article Apr 15, 2011

Mammalian EGF receptor activation by the rhomboid protease RHBDL2

Colin Adrain

Kvido Strisovsky

Markus Zettl Landian Hu Marius K Lemberg Matthew Freeman

EMBO reports Vol. 12 No. 5 pp. 421-427 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/embor.2011.50

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.

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Details

Published: Apr 15, 2011
Vol/Issue: 12(5)
Pages: 421-427
License: View

Authors

C

Colin Adrain

MRC Laboratory of Molecular Biology Hills Road Cambridge CB2 0QH UK

K

Kvido Strisovsky

MRC Laboratory of Molecular Biology Hills Road Cambridge CB2 0QH UK

M

Markus Zettl

MRC Laboratory of Molecular Biology Hills Road Cambridge CB2 0QH UK

L

Landian Hu

Molecular 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

M

Marius K Lemberg

ZMBH, DKFZ–ZMBH Allianz Im Neuenheimer Feld 282 D‐69120 Heidelberg Germany

M

Matthew Freeman

MRC Laboratory of Molecular Biology Hills Road Cambridge CB2 0QH UK

Cite This Article

Colin Adrain, Kvido Strisovsky, Markus Zettl, et al. (2011). Mammalian EGF receptor activation by the rhomboid protease RHBDL2. EMBO reports, 12(5), 421-427. https://doi.org/10.1038/embor.2011.50

Mammalian EGF receptor activation by the rhomboid protease RHBDL2

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