Monoubiquitinylation Regulates Endosomal Localization of Lst2, a Negative Regulator of EGF Receptor Signaling

• Type: Article in International Scientific Journal
• Date: 2009

Authors

Schmitt F (Author) FMUP

Journal

Title: Developmental Cell

Vol. 16

Pages: 687-698

ISSN: 1534-5807

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 24 Citations

Scopus - 25 Citations

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Authenticus ID: P-003-K2M

DOI: 10.1016/j.devcel.2009.03.015

Abstract (EN): Genetic screens performed in worms identified major regulators of the epidermal growth factor receptor (EGFR) pathway, including the ubiquitin ligase Cbl/SLI-1. Here we focus on the less-characterized Lst2 protein and confirm suppression of MAPK signals. Unexpectedly, human Lst2, a monoubiquitinylated phosphoprotein, does not localize to endosomes, despite an intrinsic phosphoinositol-binding FYVE domain. By constructing an ubiquitinylation-defective mutant and an ubiquitin fusion, we conclude that endosomal localization of Lst2, along with an ability to divert incoming EGFR molecules to degradation in lysosomes, is regulated by ubiquitinylation/deubiquitinylation cycles. Consistent with bifurcating roles, Lst2 physically binds Trim3/BERP, which interacts with Hrs and a complex that biases cargo recycling. These results establish an ubiquitin-based endosomal switch of receptor sorting, functionally equivalent to the mechanism inactivating Hrs via monoubiquitinylation.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12