Dataset Information

A quantitative proteomics screen identifies a substrate repertoire of rhomboid protease RHBDL2 in human cells and implicates it in epithelial homeostasis.

ABSTRACT: Rhomboids are intramembrane serine proteases conserved in all kingdoms of life. They regulate epidermal growth factor receptor signalling in Drosophila by releasing signalling ligands from their transmembrane tethers. Their functions in mammals are poorly understood, in part because of the lack of endogenous substrates identified thus far. We used a quantitative proteomics approach to identify the substrate repertoire of the mammalian rhomboid protease RHBDL2 in human cells. We reveal a range of novel substrates that are specifically cleaved by RHBDL2, including the interleukin-6 receptor (IL6R), cell surface protease inhibitor Spint-1, the collagen receptor tyrosine kinase DDR1, NCadherin, CLCP1/DCBLD2, KIRREL, BCAM and others. We further demonstrate that these substrates can be shed by endogenously expressed RHBDL2 and that a subset of them is resistant to shedding by cell surface metalloproteases. The expression profiles and identity of the substrates implicate RHBDL2 in physiological or pathological processes affecting epithelial homeostasis.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hek-293et Cell, Cell Culture

SUBMITTER: Jana Brezinova

LAB HEAD: Kvido Strisovsky

PROVIDER: PXD006716 | Pride | 2017-08-14

REPOSITORIES: Pride

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Quantitative proteomics screen identifies a substrate repertoire of rhomboid protease RHBDL2 in human cells and implicates it in epithelial homeostasis.

Johnson Nicholas N Březinová Jana J Stephens Elaine E Burbridge Emma E Freeman Matthew M Adrain Colin C Strisovsky Kvido K

Scientific reports 20170804 1

Rhomboids are intramembrane serine proteases conserved in all kingdoms of life. They regulate epidermal growth factor receptor signalling in Drosophila by releasing signalling ligands from their transmembrane tethers. Their functions in mammals are poorly understood, in part because of the lack of endogenous substrates identified thus far. We used a quantitative proteomics approach to investigate the substrate repertoire of rhomboid protease RHBDL2 in human cells. We reveal a range of novel subs ...[more]

PMID: 28779096

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			Action	DRS
	Homo_sapiensmEGF_sprot_all_isoforms_170303.fasta	Fasta
	KC_OF_FR12_1.RAW	Raw
	KC_OG_FR10_1.RAW	Raw
	KC_OG_FR10_2.RAW	Raw
	KC_OG_FR11_1.RAW	Raw