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Article
Nature Cell Biology 5, 410–421 (1 May 2003) | doi:10.1038/ncb975
Distinct endocytic pathways regulate TGF-|[beta]| receptor signalling and turnover
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Abstract
Endocytosis of cell surface receptors is an important regulatory event in signal transduction. The transforming growth factor β (TGF-β) 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-β 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-β 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-β receptors into distinct endocytic compartments regulates Smad activation and receptor turnover.
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