Divergence and convergence of TGF-beta/BMP signaling

J Cell Physiol. 2001 Jun;187(3):265-76. doi: 10.1002/jcp.1080.

Abstract

The transforming growth factor-beta (TGF-beta) superfamily includes more than 30 members which have a broad array of biological activities. TGF-beta superfamily ligands bind to type II and type I serine/threonine kinase receptors and transduce signals via Smad proteins. Receptor-regulated Smads (R-Smads) can be classified into two subclasses, i.e. those activated by activin and TGF-beta signaling pathways (AR-Smads), and those activated by bone morphogenetic protein (BMP) pathways (BR-Smads). The numbers of type II and type I receptors and Smad proteins are limited. Thus, signaling of the TGF-beta superfamily converges at the receptor and Smad levels. In the intracellular signaling pathways, Smads interact with various partner proteins and thereby exhibit a wide variety of biological activities. Moreover, signaling by Smads is modulated by various other signaling pathways allowing TGF-beta superfamily ligands to elicit diverse effects on target cells. Perturbations of the TGF-beta/BMP signaling pathways result in various clinical disorders including cancers, vascular diseases, and bone disorders.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / metabolism*
  • DNA-Binding Proteins / metabolism
  • Humans
  • Hypertension, Pulmonary / etiology
  • Hypertension, Pulmonary / metabolism
  • Ligands
  • Mice
  • Multigene Family
  • Protein-Serine-Threonine Kinases*
  • Receptors, Growth Factor / metabolism
  • Receptors, Transforming Growth Factor beta*
  • Signal Transduction / physiology*
  • Trans-Activators / metabolism
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Vascular Diseases / etiology
  • Vascular Diseases / metabolism

Substances

  • Bone Morphogenetic Proteins
  • DNA-Binding Proteins
  • Ligands
  • Receptors, Growth Factor
  • Receptors, Transforming Growth Factor beta
  • Trans-Activators
  • Transforming Growth Factor beta
  • Protein-Serine-Threonine Kinases