Drosophila Rhomboid-1 defines a family of putative intramembrane serine proteases

Sinisa Urban, Jeffrey R. Lee, Matthew Freeman

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)173-182
Number of pages10
JournalCell
Volume107
Issue number2
DOIs
StatePublished - Oct 19 2001
Externally publishedYes

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ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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