Structural insights into BMP receptors: Specificity, activation and inhibition

Cytokine Growth Factor Rev. 2016 Feb;27:13-34. doi: 10.1016/j.cytogfr.2015.11.005. Epub 2015 Nov 24.


Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β family (TGFβ), which signal through hetero-tetrameric complexes of type I and type II receptors. In humans there are many more TGFβ ligands than receptors, leading to the question of how particular ligands can initiate specific signaling responses. Here we review structural features of the ligands and receptors that contribute to this specificity. Ligand activity is determined by receptor-ligand interactions, growth factor prodomains, extracellular modulator proteins, receptor assembly and phosphorylation of intracellular signaling proteins, including Smad transcription factors. Detailed knowledge about the receptors has enabled the development of BMP-specific type I receptor kinase inhibitors. In future these may help to treat human diseases such as fibrodysplasia ossificans progressiva.

Keywords: BMP receptor activation; BMP receptor kinases and inhibitors; Ligand–receptor interaction; Ligand–receptor promiscuity; Protein–protein recognition.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Morphogenetic Protein Receptors* / chemistry
  • Bone Morphogenetic Protein Receptors* / metabolism
  • Bone Morphogenetic Proteins* / chemistry
  • Bone Morphogenetic Proteins* / metabolism
  • Humans
  • Myositis Ossificans / metabolism*
  • Myositis Ossificans / pathology
  • Myositis Ossificans / therapy
  • Signal Transduction*
  • Smad Proteins / metabolism
  • Structure-Activity Relationship


  • Bone Morphogenetic Proteins
  • Smad Proteins
  • Bone Morphogenetic Protein Receptors