Growth Differentiation Factor 5(GDF-5, BMP-14) is a member of the BMP family of TGFβ 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) Nterminal proregion 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-IIor Activin RII) serine/threonine kinase receptor which results in the phosphorylation and activation of cytosolic Smad proteins (Smad1, 5, and 8). GDF-5 is involved in multiple developmental processes including limb generation, cartilage development, joint formation, bone morphogenesis, cell survival, and neuritogenesis. Inhibition of GDF-5 expression or alteration of its signaling can facilitate the development of osteoarthritis.
Glial Cell Line-Derived Neurotrophic Factor (GDNF) is a disulfide-linked homodimeric glycoprotein that belongs to the TGF-β superfamily. It has been shown to promote the survival of various neuronal subpopulations in both the central as well as the peripheral nervous systems at different stages of their development. Human GDNF cDNA encodes a 211 amino acid residue prepropeptide that is processed to yield a dimeric protein. Mature human GDNF was predicted to contain two 134 amino acid residue subunits. Cells known to express GDNF include Sertoli cells, type 1 astrocytes, Schwann cells, neurons, pinealocytes and skeletal muscle cells. Mutations in this gene may be associated with Hirschsprung disease.
Glial cell line-derived neurotrophic factor(GDNF) is an important member of the GDNF family of ligands(GFL). The GDNF family of ligands is comprised by four neurotrophic factors: glial cell line-derived neurotrophic factor (GDNF), neurturin (NRTN), artemin (ARTN), and persephin (PSPN). It has been found that GFLs play a role in a number of biological processes including cell survival, neurite outgrowth, cell differentiation and cell migration. As the founding member, GDNF plays a key role in the promotion of the survival of dopaminergic neurons. GDNF is a highly conserved neurotrophic factor. The recombinant form of this protein also promotes the survival and differentiation of dopaminergic neurons in culture, and was able to prevent apoptosis of motor neurons induced by axotomy. GDNF also regulates kidney development and spermatogenesis, and it affects alcohol consumption. It has been shown that GDNF results in two Parkinson's disease clinical trial and in a number of animal trials. It has been taken as a potent survival factor for central motoneurons.
This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. The recombinant form of this protein, a highly conserved neurotrophic factor, was shown to promote the survival and differentiation of dopaminergic neurons in culture, and was able to prevent apoptosis of motor neurons induced by axotomy. This protein is a ligand for the product of the RET (rearranged during transfection) protooncogene. Mutations in this gene may be associated with Hirschsprung disease and Tourette syndrome. This gene encodes multiple protein isoforms that may undergo similar proteolytic processing.
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