Conservation of intramembrane proteolytic activity and substrate specificity in prokaryotic and eukaryotic rhomboids

Sinisa Urban, Daniel Schlieper, Matthew Freeman

Research output: Contribution to journalArticle

Abstract

Rhomboid is an intramembrane serine protease responsible for the proteolytic activation of Drosophila epidermal growth factor receptor (EGFR) ligands [1]. Although nothing is known about the function of the ∼100 currently known rhomboid genes conserved throughout evolution, a recent analysis suggests that a Rhomboid from the pathogenic bacterium Providencia stuartii is involved in the production of a quorum-sensing factor [2]. This suggests that an intercellular signaling mechanism may have been conserved between prokaryotes and metazoans [3]. However, the function of prokaryotic Rhomboids is unknown. We have examined the ability of eight prokaryotic Rhomboids to cleave the three Drosophila EGFR ligands. Despite their striking sequence divergence, Rhomboids from one Gram-positive and four Gram-negative species, including Providencia, specifically cleaved Drosophila substrates, but not similar proteins such as Transforming Growth Factor (α (TGFα) and Delta. Although the sequence similarity between these divergent Rhomboids is very limited, all contain the putative serine catalytic triad residues, and their specific mutation abolished protease activity. Therefore, despite low overall homology, the Rhomboids are a family of ancient, functionally conserved intramembrane serine proteases, some of which also have conserved substrate specificity. Moreover, a function for Rhomboids in activating intercellular signaling appears to have evolved early.

Original languageEnglish (US)
Pages (from-to)1507-1512
Number of pages6
JournalCurrent Biology
Volume12
Issue number17
DOIs
StatePublished - Sep 3 2002
Externally publishedYes

Fingerprint

substrate specificity
Substrate Specificity
Providencia
Drosophila
Conservation
Serine Proteases
serine proteinases
Epidermal Growth Factor Receptor
Providencia stuartii
Substrates
Ligands
Quorum Sensing
transforming growth factors
quorum sensing
Transforming Growth Factors
prokaryotic cells
serine
Serine
Bacteria
Peptide Hydrolases

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Conservation of intramembrane proteolytic activity and substrate specificity in prokaryotic and eukaryotic rhomboids. / Urban, Sinisa; Schlieper, Daniel; Freeman, Matthew.

In: Current Biology, Vol. 12, No. 17, 03.09.2002, p. 1507-1512.

Research output: Contribution to journalArticle

Urban, Sinisa ; Schlieper, Daniel ; Freeman, Matthew. / Conservation of intramembrane proteolytic activity and substrate specificity in prokaryotic and eukaryotic rhomboids. In: Current Biology. 2002 ; Vol. 12, No. 17. pp. 1507-1512.
@article{06be1576e925419896c88cea0df79f8a,
title = "Conservation of intramembrane proteolytic activity and substrate specificity in prokaryotic and eukaryotic rhomboids",
abstract = "Rhomboid is an intramembrane serine protease responsible for the proteolytic activation of Drosophila epidermal growth factor receptor (EGFR) ligands [1]. Although nothing is known about the function of the ∼100 currently known rhomboid genes conserved throughout evolution, a recent analysis suggests that a Rhomboid from the pathogenic bacterium Providencia stuartii is involved in the production of a quorum-sensing factor [2]. This suggests that an intercellular signaling mechanism may have been conserved between prokaryotes and metazoans [3]. However, the function of prokaryotic Rhomboids is unknown. We have examined the ability of eight prokaryotic Rhomboids to cleave the three Drosophila EGFR ligands. Despite their striking sequence divergence, Rhomboids from one Gram-positive and four Gram-negative species, including Providencia, specifically cleaved Drosophila substrates, but not similar proteins such as Transforming Growth Factor (α (TGFα) and Delta. Although the sequence similarity between these divergent Rhomboids is very limited, all contain the putative serine catalytic triad residues, and their specific mutation abolished protease activity. Therefore, despite low overall homology, the Rhomboids are a family of ancient, functionally conserved intramembrane serine proteases, some of which also have conserved substrate specificity. Moreover, a function for Rhomboids in activating intercellular signaling appears to have evolved early.",
author = "Sinisa Urban and Daniel Schlieper and Matthew Freeman",
year = "2002",
month = "9",
day = "3",
doi = "10.1016/S0960-9822(02)01092-8",
language = "English (US)",
volume = "12",
pages = "1507--1512",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "17",

}

TY - JOUR

T1 - Conservation of intramembrane proteolytic activity and substrate specificity in prokaryotic and eukaryotic rhomboids

AU - Urban, Sinisa

AU - Schlieper, Daniel

AU - Freeman, Matthew

PY - 2002/9/3

Y1 - 2002/9/3

N2 - Rhomboid is an intramembrane serine protease responsible for the proteolytic activation of Drosophila epidermal growth factor receptor (EGFR) ligands [1]. Although nothing is known about the function of the ∼100 currently known rhomboid genes conserved throughout evolution, a recent analysis suggests that a Rhomboid from the pathogenic bacterium Providencia stuartii is involved in the production of a quorum-sensing factor [2]. This suggests that an intercellular signaling mechanism may have been conserved between prokaryotes and metazoans [3]. However, the function of prokaryotic Rhomboids is unknown. We have examined the ability of eight prokaryotic Rhomboids to cleave the three Drosophila EGFR ligands. Despite their striking sequence divergence, Rhomboids from one Gram-positive and four Gram-negative species, including Providencia, specifically cleaved Drosophila substrates, but not similar proteins such as Transforming Growth Factor (α (TGFα) and Delta. Although the sequence similarity between these divergent Rhomboids is very limited, all contain the putative serine catalytic triad residues, and their specific mutation abolished protease activity. Therefore, despite low overall homology, the Rhomboids are a family of ancient, functionally conserved intramembrane serine proteases, some of which also have conserved substrate specificity. Moreover, a function for Rhomboids in activating intercellular signaling appears to have evolved early.

AB - Rhomboid is an intramembrane serine protease responsible for the proteolytic activation of Drosophila epidermal growth factor receptor (EGFR) ligands [1]. Although nothing is known about the function of the ∼100 currently known rhomboid genes conserved throughout evolution, a recent analysis suggests that a Rhomboid from the pathogenic bacterium Providencia stuartii is involved in the production of a quorum-sensing factor [2]. This suggests that an intercellular signaling mechanism may have been conserved between prokaryotes and metazoans [3]. However, the function of prokaryotic Rhomboids is unknown. We have examined the ability of eight prokaryotic Rhomboids to cleave the three Drosophila EGFR ligands. Despite their striking sequence divergence, Rhomboids from one Gram-positive and four Gram-negative species, including Providencia, specifically cleaved Drosophila substrates, but not similar proteins such as Transforming Growth Factor (α (TGFα) and Delta. Although the sequence similarity between these divergent Rhomboids is very limited, all contain the putative serine catalytic triad residues, and their specific mutation abolished protease activity. Therefore, despite low overall homology, the Rhomboids are a family of ancient, functionally conserved intramembrane serine proteases, some of which also have conserved substrate specificity. Moreover, a function for Rhomboids in activating intercellular signaling appears to have evolved early.

UR - http://www.scopus.com/inward/record.url?scp=0037015265&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037015265&partnerID=8YFLogxK

U2 - 10.1016/S0960-9822(02)01092-8

DO - 10.1016/S0960-9822(02)01092-8

M3 - Article

C2 - 12225666

AN - SCOPUS:0037015265

VL - 12

SP - 1507

EP - 1512

JO - Current Biology

JF - Current Biology

SN - 0960-9822

IS - 17

ER -