Bone morphogenetic proteins signal through the transforming growth factor-beta type III receptor.
The bone morphogenetic protein (BMP) family, the largest subfamily of the structurally conserved transforming growth factor-beta (TGF-beta) superfamily of growth factors, are multifunctional regulators of development, proliferation, and differentiation. The TGF-beta type III receptor (TbetaRIII or betaglycan) is an abundant cell surface proteoglycan that has been well characterized as a TGF-beta and inhibin receptor. Here we demonstrate that TbetaRIII functions as a BMP cell surface receptor. TbetaRIII directly and specifically binds to multiple members of the BMP subfamily, including BMP-2, BMP-4, BMP-7, and GDF-5, with similar kinetics and ligand binding domains as previously identified for TGF-beta. TbetaRIII also enhances ligand binding to the BMP type I receptors, whereas short hairpin RNA-mediated silencing of endogenous TbetaRIII attenuates BMP-mediated Smad1 phosphorylation. Using a biologically relevant model for TbetaRIII function, we demonstrate that BMP-2 specifically stimulates TbetaRIII-mediated epithelial to mesenchymal cell transformation. The ability of TbetaRIII to serve as a cell surface receptor and mediate BMP, inhibin, and TGF-beta signaling suggests a broader role for TbetaRIII in orchestrating TGF-beta superfamily signaling.
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Related Subject Headings
- Transforming Growth Factor beta
- Smad1 Protein
- Signal Transduction
- Receptors, Transforming Growth Factor beta
- Proteoglycans
- Protein Binding
- Phosphorylation
- Kinetics
- Inhibins
- Humans
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transforming Growth Factor beta
- Smad1 Protein
- Signal Transduction
- Receptors, Transforming Growth Factor beta
- Proteoglycans
- Protein Binding
- Phosphorylation
- Kinetics
- Inhibins
- Humans