Regulated intracellular ligand transport and proteolysis control EGF signal activation in Drosophila

Jeffrey R. Lee, Sinisa Urban, Clare F. Garvey, Matthew Freeman

Research output: Contribution to journalArticle

Abstract

The membrane proteins Star and Rhomboid-1 have been genetically defined as the primary regulators of EGF receptor activation in Drosophila, but their molecular mechanisms have been elusive. Both Star and Rhomboid-1 have been assumed to work at the cell surface to control ligand activation. Here, we demonstrate that they control receptor signaling by regulating intracellular trafficking and proteolysis of the ligand Spitz. Star is present throughout the secretory pathway and is required to export Spitz from the endoplasmic reticulum to the Golgi apparatus. Rhomboid-1 is localized in the Golgi, where it promotes the cleavage of Spitz. This defines a novel growth factor release mechanism that is distinct from metalloprotease-dependent shedding from the cell surface.

Original languageEnglish (US)
Pages (from-to)161-171
Number of pages11
JournalCell
Volume107
Issue number2
DOIs
StatePublished - Oct 19 2001
Externally publishedYes

Fingerprint

Proteolysis
Epidermal Growth Factor
Drosophila
Stars
Chemical activation
Ligands
Secretory Pathway
Golgi Apparatus
Metalloproteases
Epidermal Growth Factor Receptor
Endoplasmic Reticulum
Intercellular Signaling Peptides and Proteins
Membrane Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Regulated intracellular ligand transport and proteolysis control EGF signal activation in Drosophila. / Lee, Jeffrey R.; Urban, Sinisa; Garvey, Clare F.; Freeman, Matthew.

In: Cell, Vol. 107, No. 2, 19.10.2001, p. 161-171.

Research output: Contribution to journalArticle

Lee, Jeffrey R. ; Urban, Sinisa ; Garvey, Clare F. ; Freeman, Matthew. / Regulated intracellular ligand transport and proteolysis control EGF signal activation in Drosophila. In: Cell. 2001 ; Vol. 107, No. 2. pp. 161-171.
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