Members of the glial cell line-derived neurotrophic factor (GDNF) family, including GDNF and neurturin (NTN), play key roles in the control of vertebrate neuron survival and differentiation. Physiological responses to NTN require the presence of a novel glycosylphosphadidylinositol linked protein NTNRα, which is a cell surface receptor for NTN. The cDNAs encoding NTNRa from human, rat, chicken, and mouse have been cloned recently. NTNRα was also termed GDNFRβ, Ret ligand 2 (RETL2) or TGFβ-related neurotrophic factor receptor 2 (TrnR2) and nominated as GFRα-2 recently. GFRα-2 binds NTN and mediates activation of RET receptor tyrosine kinase by both NTN and GDNF. Thus, NTN, GFRα-2, and the Ret PTK form a complex to transduce NTN signal and to mediate NTN function.
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