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Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2001 Mar 02; Vol. 276 (9), pp. 6727-38. Date of Electronic Publication: 2000 Dec 01. - Publication Year :
- 2001
-
Abstract
- Transforming growth factor-beta (TGF-beta) signaling proceeds from the cell membrane to the nucleus through the cooperation of the type I and II serine/threonine kinase receptors and their downstream SMAD effectors. Although various regulatory proteins affecting TGF-beta-mediated events have been described, relatively little is known about receptor interactions at the level of the plasma membrane. Caveolae are cholesterol-rich membrane microdomains that, along with their marker protein caveolin-1 (Cav-1), have been implicated in the compartmentalization and regulation of certain signaling events. Here, we demonstrate that specific components of the TGF-beta cascade are associated with caveolin-1 in caveolae and that Cav-1 interacts with the Type I TGF-beta receptor. Additionally, Cav-1 is able to suppress TGF-beta-mediated phosphorylation of Smad-2 and subsequent downstream events. We localize the Type I TGF-beta receptor interaction to the scaffolding domain of Cav-1 and show that it occurs in a physiologically relevant time frame, acting to rapidly dampen signaling initiated by the TGF-beta receptor complex.
- Subjects :
- 3T3 Cells
Amino Acid Sequence
Animals
Binding Sites
Caveolin 1
Cell Differentiation
DNA-Binding Proteins chemistry
Mice
Molecular Sequence Data
Phosphorylation
Receptors, Transforming Growth Factor beta analysis
Smad2 Protein
Tacrolimus Binding Protein 1A physiology
Trans-Activators chemistry
Caveolins physiology
DNA-Binding Proteins physiology
Receptors, Transforming Growth Factor beta physiology
Trans-Activators physiology
Transforming Growth Factor beta physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 276
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 11102446
- Full Text :
- https://doi.org/10.1074/jbc.M008340200