Specificity, diversity, and regulation in TGF-beta superfamily signaling

FASEB J. 1999 Dec;13(15):2105-24.


Transforming growth factor-beta (TGF-beta) superfamily members are multifunctional cell-cell signaling proteins that play pivotal roles in tissue homeostasis and development of multicellular animals. They mediate their pleiotropic effects from membrane to nucleus through distinct combinations of type I and type II serine/threonine kinase receptors and their downstream effectors, known as Smad proteins. Certain Smads, termed receptor-regulated Smads, become phosphorylated by activated type I receptors and form heteromeric complexes with a common-partner Smad4, which translocates into the nucleus to control gene transcription. In addition to these signal transducing Smads, inhibitory Smads have been identified that inhibit the activation of receptor-regulated Smads. In contrast to the still growing TGF-beta superfamily (with approximately 30 members in mammals), relatively few type I and type II receptors as well as Smads have been identified. We will focus on recent insights into the molecular mechanisms by which signaling specificity between different TGF-beta superfamily members is achieved and regulated, and how a single family member can elicit a broad scala of biological responses.-Piek, E., Heldin, C.-H., ten Dijke, P. Specificity, diversity, and regulation in TGF-beta superfamily signaling.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Protein Isoforms / metabolism
  • Protein-Serine-Threonine Kinases*
  • Receptors, Growth Factor / metabolism*
  • Receptors, Transforming Growth Factor beta*
  • Signal Transduction*
  • Transcription Factors / metabolism
  • Transforming Growth Factor beta / metabolism*


  • Protein Isoforms
  • Receptors, Growth Factor
  • Receptors, Transforming Growth Factor beta
  • Transcription Factors
  • Transforming Growth Factor beta
  • Protein-Serine-Threonine Kinases