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.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Di Guglielmo GM,Le Roy C,Goodfellow AF,Wrana JLdoi
10.1038/ncb975keywords:
subject
Has Abstractpub_date
2003-05-01 00:00:00pages
410-21issue
5eissn
1465-7392issn
1476-4679pii
ncb975journal_volume
5pub_type
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