Extracellular regulation of BMP signaling in vertebrates: a cocktail of modulators

Dev Biol. 2002 Oct 15;250(2):231-50.


The transforming growth factor-beta (TGF-beta) superfamily contains a variety of growth factors which all share common sequence elements and structural motifs. These proteins are known to exert a wide spectrum of biological responses on a large variety of cell types in both vertebrates and invertebrates. Many of them have important functions during embryonic development in pattern formation and tissue specification, and in adult tissues, they are involved in processes such as wound healing, bone repair, and bone remodeling. The family is divided into two general branches: the BMP/GDF and the TGF-beta/Activin/Nodal branches, whose members have diverse, often complementary effects. It is obvious that an orchestered regulation of different actions of these proteins is necessary for proper functioning. The TGF-beta family members act by binding extracellularly to a complex of serine/threonine kinase receptors, which consequently activate Smad molecules by phosphorylation. These Smads translocate to the nucleus, where they modulate transcription of specific genes. Three levels by which this signaling pathway is regulated could be distinguished. First, a control mechanism exists in the intracellular space, where inhibitory Smads and Smurfs prevent further signaling and activation of target genes. Second, at the membrane site, the pseudoreceptor BAMBI/Nma is able to inhibit further signaling within the cells. Finally, a range of extracellular mediators are identified which modulate the functioning of members of the TGF-beta superfamily. Here, we review the insights in the extracellular regulation of members of the BMP subfamily of secreted growth factors with a major emphasis on vertebrate BMP modulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / physiology*
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cytokines
  • Extracellular Space / physiology
  • Follistatin / physiology
  • Follistatin-Related Proteins / physiology
  • Glycoproteins*
  • Intercellular Signaling Peptides and Proteins*
  • Models, Biological
  • Molecular Sequence Data
  • Proteins / physiology
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Vertebrates / genetics
  • Vertebrates / growth & development
  • Vertebrates / physiology
  • Xenopus Proteins


  • Bone Morphogenetic Proteins
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cytokines
  • Follistatin
  • Follistatin-Related Proteins
  • Glycoproteins
  • Grem2 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Nbl1 protein, mouse
  • Proteins
  • Xenopus Proteins
  • cer1 protein, Xenopus
  • noggin protein
  • chordin