Bone morphogenetic proteins signal through the transforming growth factor-beta type III receptor.

Kirkbride KC, Townsend TA, Bruinsma MW, Barnett JV, Blobe GC
J Biol Chem. 2008 283 (12): 7628-37

PMID: 18184661 · DOI:10.1074/jbc.M704883200

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.

MeSH Terms (14)

Animals Bone Morphogenetic Proteins Cercopithecus aethiops COS Cells Humans Inhibins Kinetics Phosphorylation Protein Binding Proteoglycans Receptors, Transforming Growth Factor beta Signal Transduction Smad1 Protein Transforming Growth Factor beta

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