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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2003-5-1
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pubmed:abstractText |
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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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transforming Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD7 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/SMURF2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Smad2 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad7 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Vesicular Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ZFYVE16 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/early endosome antigen 1
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1465-7392
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
5
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
410-21
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12717440-Animals,
pubmed-meshheading:12717440-Carrier Proteins,
pubmed-meshheading:12717440-Caveolae,
pubmed-meshheading:12717440-Cell Compartmentation,
pubmed-meshheading:12717440-Cells, Cultured,
pubmed-meshheading:12717440-Clathrin-Coated Vesicles,
pubmed-meshheading:12717440-DNA-Binding Proteins,
pubmed-meshheading:12717440-Endocytosis,
pubmed-meshheading:12717440-Endosomes,
pubmed-meshheading:12717440-Eukaryotic Cells,
pubmed-meshheading:12717440-Fluorescent Antibody Technique,
pubmed-meshheading:12717440-Humans,
pubmed-meshheading:12717440-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:12717440-Ligases,
pubmed-meshheading:12717440-Membrane Microdomains,
pubmed-meshheading:12717440-Membrane Proteins,
pubmed-meshheading:12717440-Microscopy, Electron,
pubmed-meshheading:12717440-Protein Transport,
pubmed-meshheading:12717440-Receptors, Transforming Growth Factor beta,
pubmed-meshheading:12717440-Serine Endopeptidases,
pubmed-meshheading:12717440-Signal Transduction,
pubmed-meshheading:12717440-Smad2 Protein,
pubmed-meshheading:12717440-Smad7 Protein,
pubmed-meshheading:12717440-Trans-Activators,
pubmed-meshheading:12717440-Ubiquitin-Protein Ligases,
pubmed-meshheading:12717440-Vesicular Transport Proteins
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pubmed:year |
2003
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pubmed:articleTitle |
Distinct endocytic pathways regulate TGF-beta receptor signalling and turnover.
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pubmed:affiliation |
Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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