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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2009

Autores

Schmitt F (Autor) FMUP

Revista

Título: Developmental Cell

Vol. 16

Páginas: 687-698

ISSN: 1534-5807

Editora: Elsevier

Indexação

ISI Web of Knowledge - 24 Citações

Scopus - 25 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Outras ciências médicas

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12