Reference Report

Reference
Citation	Urban, S., Lee, J.R., Freeman, M. (2002). A family of Rhomboid intramembrane proteases activates all Drosophila membrane-tethered EGF ligands. EMBO J. 21(16): 4277--4286. (Export to RIS)
FlyBase ID	FBrf0151285
Publication Type	Research paper
PubMed ID	12169630
PubMed Abstract	Drosophila has three membrane-tethered epidermal growth factor (EGF)-like proteins: Spitz, Gurken and Keren. Spitz and Gurken have been genetically confirmed to activate the EGF receptor, but Keren is uncharacterized. Spitz is activated by regulated intracellular translocation and cleavage by the transmembrane proteins Star and the protease Rhomboid-1, respectively. Rhomboid-1 is a member of a family of seven similar proteins in Drosophila. We have analysed four of these: all are proteases that can cleave Spitz, Gurken and Keren, and all activate only EGF receptor signalling in vivo. Star acts as an endoplasmic reticulum (ER) export factor for all three. The importance of this translocation is highlighted by the fact that when Spitz is cleaved by Rhomboids in the ER it cannot be secreted. Keren activates the EGF receptor in vivo, providing strong evidence that it is a true ligand. Our data demonstrate that all membrane-tethered EGF ligands in Drosophila are activated by the same strategy of cleavage by Rhomboids, which are ancient and widespread intramembrane proteases. This is distinct from the metalloprotease-induced activation of mammalian EGF-like ligands.
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Language of Publication	English
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Publication Type	Journal
Abbreviation	EMBO J.
Title	The EMBO Journal
Publication Year	1982-
ISBN/ISSN	0261-4189
Data from Reference
Alleles (10)
	Krn^{s.Scer\UAS.cUa} Krn^Scer\UAS.cUa rho-4^Scer\UAS.cUa rho^{Scer\UAS.cdCa} ru^Scer\UAS.cWa S^Scer\UAS.cGa Scer\GAL4^arm.PS Scer\GAL4^Bx-MS1096 spi^s.Scer\UAS stet^Scer\UAS.cUa
Constructs (9)
	P{GAL4-arm.S} P{UAS-Krn.s.U} P{UAS-Krn.U} P{UAS-rho-4.U} P{UAS-ru.W} P{UAS-spi.s} P{UAS-Star} P{UAS-stet.U} P{UAS-ve.dC}
Genes (8)
	Krn rho rho-4 ru S Scer\GAL4 spi stet
Insertions (1)
	P{GawB}Bx^MS1096