A family of Rhomboiproteases activates all Drosod intramembrane phila membrane-tethered EGF ligands

AUTOR(ES)

Urban, Sinisa

FONTE

Oxford University Press

RESUMO

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.

Documentos Relacionados

• Computational prediction of membrane-tethered transcription factors
• Receptor-mediated endocytosis of soluble and membrane-tethered Sonic hedgehog by Patched-1
• Activation and inhibition of G protein-coupled receptors by cell-penetrating membrane-tethered peptides
• The tethered configuration of the EGF receptor extracellular domain exerts only a limited control of receptor function
• All in the Family