A single heteromeric receptor complex is sufficient to mediate biological effects of transforming growth factor-beta ligands.
Transforming growth factor beta (TGF-beta), a multifunctional cytokine that regulates a variety of biological functions, signals through a heteromeric receptor complex of the type I and type II TGF-beta receptors. The type II receptor, a transmembrane serine-threonine kinase, was cloned based on its ability to directly bind TGF-beta. Recently, a number of candidate type I TGF-beta receptors have been isolated. Although only one of these transmembrane kinases (R4) has been shown to mediate TGF-beta-dependent gene activation, others bind TGF-beta when overexpressed in COS cells. Consequently, it has been postulated that the diversity of TGF-beta responses is generated through the association of distinct type I receptors with the type II TGF-beta receptor, thus creating receptor complexes of differential signaling capacities. In contrast to this model, we demonstrate that stable expression of only the R4 type I TGF-beta receptor in a mutant cell line lacking endogenous type I TGF-beta receptor was able to complex with the endogenous type II TGF-beta receptor and restore the effects of TGF-beta on inhibition of cell proliferation and activation of specific genes, regardless of which of the three mammalian isoforms of TGF-beta was used as the ligand. Therefore, R4 acts as a fully functional type I TGF-beta receptor, and the differential effects of TGF-beta are likely mediated by a single receptor complex consisting of R4 and the type II receptor.
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Related Subject Headings
- Transforming Growth Factor beta
- Receptors, Transforming Growth Factor beta
- Mink
- Ligands
- Cell Line
- Biochemistry & Molecular Biology
- Animals
- 34 Chemical sciences
- 32 Biomedical and clinical sciences
- 31 Biological sciences
Citation
Published In
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transforming Growth Factor beta
- Receptors, Transforming Growth Factor beta
- Mink
- Ligands
- Cell Line
- Biochemistry & Molecular Biology
- Animals
- 34 Chemical sciences
- 32 Biomedical and clinical sciences
- 31 Biological sciences