1. Recombinant Proteins
  2. Cytokines and Growth Factors
  3. TGF-beta Superfamily Neurotrophic Factors
  4. GDNF family

The glial cell line-derived (GDNF) family ligands (GFLs) of neurotrophic factors include 4 closely related proteins: GDNF, neurturin (NRTN), artemin (ARTN), and persephin (PSPN). Growth/differentiation factor 15 (GDF15), a protein of the TGF-β superfamily, is a distant member of GFL. It is worth noting that all the GDNF family proteins are distant members of the TGF-β superfamily. GFLs signal mainly through transmembrane receptor tyrosine kinase RET via forming a tripartite complex. GFLs form homodimer and bind to respective co-receptor GDNF family receptor alpha (GFRα 1-4) and GDNF family receptor α-like (GFRAL) respectively. GDNF preferentially binds to GFRα1, NRTN to GFRα2, ARTN to GFRα3, and PSPN to GFRα4. In addition, NRTN, ARNT, and PSPN can all exert their biological effects via GFRα1. GDF15 binds to GFRAL and does not seem to have affinity to GFRα co-receptors. The complex of ligand and co-receptor interacts with RET which leads to phosphorylation of RET and activation of intracellular signalling cascades and enzymatic pathways, such as JAK/Stat, PI3K/Akt, MAPK, JNK, RAC1, VAV2, PLCγ. GFLs play a role in a number of biological processes including cell survival, neurite outgrowth, cell differentiation and cell migration.

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