Distinct endocytic pathways regulate TGF-beta receptor signalling and turnover.
Nat Cell Biol
; 5(5): 410-21, 2003 May.
Article
em En
| MEDLINE
| ID: mdl-12717440
ABSTRACT
Endocytosis of cell surface receptors is an important regulatory event in signal transduction. The transforming growth factor beta (TGF-beta) superfamily signals to the Smad pathway through heteromeric Ser-Thr kinase receptors that are rapidly internalized and then downregulated in a ubiquitin-dependent manner. Here we demonstrate that TGF-beta receptors internalize into both caveolin- and EEA1-positive vesicles and reside in both lipid raft and non-raft membrane domains. Clathrin-dependent internalization into the EEA1-positive endosome, where the Smad2 anchor SARA is enriched, promotes TGF-beta signalling. In contrast, the lipid raft-caveolar internalization pathway contains the Smad7-Smurf2 bound receptor and is required for rapid receptor turnover. Thus, segregation of TGF-beta receptors into distinct endocytic compartments regulates Smad activation and receptor turnover.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Serina Endopeptidases
/
Transdução de Sinais
/
Compartimento Celular
/
Receptores de Fatores de Crescimento Transformadores beta
/
Cavéolas
/
Microdomínios da Membrana
/
Transporte Proteico
/
Peptídeos e Proteínas de Sinalização Intracelular
/
Endocitose
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Cell Biol
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Canadá