Structural studies of the TGF-βs and their receptors - insights into evolution of the TGF-β superfamily

FEBS Lett. 2012 Jul 4;586(14):1860-70. doi: 10.1016/j.febslet.2012.05.028. Epub 2012 May 28.

Abstract

TGF-βs are small secreted signaling proteins that function as vital regulators of cellular growth and differentiation. They signal through a single pair of receptors, known as TβR-I and TβR-II, and are among the most recently evolved members of the signaling superfamily to which they belong. This review provides an overview of the TGF-β, BMP, and activin receptor complexes that have been determined over the past several years. These structures underscore the shared ancestry of the TGF-βs with the BMPs and activins, but also provide insight as to how the TGF-βs diverged from the BMPs and activins to bind and assemble their receptors in a distinct manner. These distinctive modes of receptor binding engender the TGF-βs with high specificity for their receptors and allow them to fulfill their essential functions in vivo without interference from the many other proteins of the superfamily.

Publication types

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

MeSH terms

  • Activin Receptors / metabolism
  • Activins / metabolism
  • Animals
  • Bone Morphogenetic Proteins / metabolism
  • Evolution, Molecular
  • Humans
  • Models, Biological
  • Models, Molecular
  • Molecular Conformation
  • Phylogeny
  • Protein Binding
  • Protein Conformation
  • Protein Serine-Threonine Kinases / metabolism
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / metabolism
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism*

Substances

  • Bone Morphogenetic Proteins
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Activins
  • Protein Serine-Threonine Kinases
  • Activin Receptors
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II