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

J Biol Chem. 2008 Mar 21;283(12):7628-37. doi: 10.1074/jbc.M704883200. Epub 2008 Jan 9.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / metabolism*
  • COS Cells
  • Chlorocebus aethiops
  • Humans
  • Inhibins / metabolism*
  • Kinetics
  • Phosphorylation
  • Protein Binding
  • Proteoglycans / metabolism*
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Signal Transduction / physiology*
  • Smad1 Protein / metabolism
  • Transforming Growth Factor beta / metabolism*

Substances

  • Bone Morphogenetic Proteins
  • Proteoglycans
  • Receptors, Transforming Growth Factor beta
  • SMAD1 protein, human
  • Smad1 Protein
  • Transforming Growth Factor beta
  • betaglycan
  • Inhibins