Recombinant Human GFR alpha-1 Fc Chimera Protein, CF

Glial cell line-derived growth factor (GDNF), neurturin (NTN), artemin and persephin are distant members of the TGF-beta  superfamily. They function as neurotrophic factors for a variety of neuronal populations in the central and peripheral nervous systems. The bioactivities of GDNF and NTN are mediated through a receptor complex composed of the non ligand-binding signaling subunit (c-Ret receptor tyrosine kinase) and either of two ligand binding subunits [GDNF receptor alpha-1 (GFR alpha-1) or GFR alpha-2]. GFR alpha-1 and -2 are members of a family of at least four cysteine-rich glycosyl-phosphatidylinositol (GPI)-linked cell surface proteins that share conserved placements of many of their cysteine residues. Binding of GDNF to membrane‑associated GFR alpha-1 or GFR alpha-2 initiates the association with and activation of the Ret tyrosine kinase. Soluble GFR alphas released enzymatically from the cell surface-associated protein with phosphatidylinositol phospholipase C, as well as recombinantly produced soluble GFR alpha-1, can also bind with high-affinity to GDNF and trigger the activation of Ret tyrosine kinase.

Human GFR alpha-1 cDNA encodes a 465 amino acid (aa) residue protein with an N-terminal 24 aa residue hydrophobic signal peptide. Like other GPI-linked proteins, human GFR alpha-1 has a C-terminal hydrophobic region which is preceded by a three aa residue (ASS) GPI-binding site. Human GFR alpha-1 shares 93% aa identity with rat GFR alpha-1. The expression of the various GFR alphas are differentially regulated in the central and peripheral nervous system, suggesting complementary roles for the GFR alphas in mediating the activities of the GDNF family of neurotrophic factors.