Growth Differentiation Factor-5 (GDF-5; also called BMP-14 and CDMP-1) is a member of the BMP family of TGF-beta superfamily proteins. Human GDF-5, -6, and -7 are a defined subgroup of the BMP family. GDF-5 is synthesized as a homodimeric precursor protein consisting of a 354 amino acid (aa) N-terminal pro-region and a 120 aa C-terminal mature peptide. Mature human GDF-5 shares 99% aa sequence identity with both mature mouse and rat GDF-5. GDF-5 signaling is mediated by formation of a heterodimeric complex consisting of a type 1 (BMPR-IB) and a type II (BMPR-II or Activin RII) serine/threonine kinase receptor which results in the phosphorylation and activation of cytosolic Smad proteins (Smad1, 5, and 8). Similar to other BMP family proteins, GDF-5 signaling is antagonized by Noggin. GDF-5 is involved in multiple developmental processes including limb generation, cartilage development, joint formation, bone morphogenesis, cell survival, and neuritogenesis.
