TY - JOUR
T1 - Drosophila Rhomboid-1 defines a family of putative intramembrane serine proteases
AU - Urban, Sinisa
AU - Lee, Jeffrey R.
AU - Freeman, Matthew
N1 - Funding Information:
We thank Mariann Bienz, Brian Hartley, Richard Henderson, Peter Lawrence, Sean Munro, and Gillian Murphy for helpful discussion and advice. Sumio Sugano (University of Tokyo) provided the RHBDL2 cDNA. Sean Munro, Birgitta Olofsson, Rosanna Baker, Katherine Brown, and Angus MacQuibban made helpful suggestions about the manuscript. S.U. was partly supported by an NSERC (Canada) scholarship and a Trinity College Cambridge external research studentship. J.R.L. was partly supported by an NSERC (Canada) scholarship and the Cambridge Commonwealth Trust.
PY - 2001/10/19
Y1 - 2001/10/19
N2 - The polytopic membrane protein Rhomboid-1 promotes the cleavage of the membrane-anchored TGFα-like growth factor Spitz, allowing it to activate the Drosophila EGF receptor. Until now, the mechanism of this key signaling regulator has been obscure, but our analysis suggests that Rhomboid-1 is a novel intramembrane serine protease that directly cleaves Spitz. In accordance with the putative Rhomboid active site being in the membrane bilayer, Spitz is cleaved within its transmembrane domain, and thus is, to our knowledge, the first example of a growth factor activated by regulated intramembrane proteolysis. Rhomboid-1 is conserved throughout evolution from archaea to humans, and our results show that a human Rhomboid promotes Spitz cleavage by a similar mechanism. This growth factor activation mechanism may therefore be widespread.
AB - The polytopic membrane protein Rhomboid-1 promotes the cleavage of the membrane-anchored TGFα-like growth factor Spitz, allowing it to activate the Drosophila EGF receptor. Until now, the mechanism of this key signaling regulator has been obscure, but our analysis suggests that Rhomboid-1 is a novel intramembrane serine protease that directly cleaves Spitz. In accordance with the putative Rhomboid active site being in the membrane bilayer, Spitz is cleaved within its transmembrane domain, and thus is, to our knowledge, the first example of a growth factor activated by regulated intramembrane proteolysis. Rhomboid-1 is conserved throughout evolution from archaea to humans, and our results show that a human Rhomboid promotes Spitz cleavage by a similar mechanism. This growth factor activation mechanism may therefore be widespread.
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U2 - 10.1016/S0092-8674(01)00525-6
DO - 10.1016/S0092-8674(01)00525-6
M3 - Article
C2 - 11672525
AN - SCOPUS:0035913908
SN - 0092-8674
VL - 107
SP - 173
EP - 182
JO - Cell
JF - Cell
IS - 2
ER -