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

被引：310

作者：

Lee, JR ^{[1
]}

Urban, S ^{[1
]}

Garvey, CF ^{[1
]}

Freeman, M ^{[1
]}

机构：

[1] MRC, Mol Biol Lab, Cambridge CB2 2QH, England

来源：

CELL | 2001年 / 107卷 / 02期

基金：

加拿大自然科学与工程研究理事会;

关键词：

D O I：

10.1016/S0092-8674(01)00526-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：161 / 171

页数：11

共 40 条

[1] Diverse cell surface protein ectodomains are shed by a system sensitive to metalloprotease inhibitors [J].