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The GDNF/Neurturin‐Ret multicomponent receptor system
Author(s) -
Takahashi Masahide,
Nakayama Seiko
Publication year - 1998
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/j.1440-1789.1998.tb00092.x
Subject(s) - glial cell line derived neurotrophic factor , neurturin , gdnf family of ligands , proto oncogene proteins c ret , neurotrophic factors , biology , receptor tyrosine kinase , microbiology and biotechnology , tyrosine kinase , neuroscience , receptor , neurotrophin , cancer research , signal transduction , genetics
Glial cell line‐derived neurotrophic factor (GDNF) and neurturin (NTN) are structurally related neurotrophic factors that play crucial roles in the survival of peripheral sensory, sympathetic and dopaminergic neurons as well as motoneurons. Glial cell line‐derived neurotrophic factordeficient mice showed lack of enteric neurons and renal agenesis or dysgenesis. Surprisingly, this phenotype was strikingly similar to that of ret proto‐oncogene‐deficient mice, suggesting that Ret tyrosine kinase might be a functional receptor for GDNF. Recent studies demonstrated that both GDNF and NTN were able to induce Ret tyrosine phosphorylation although they did not bind to Ret with high affinity, but novel glycosyl‐phosphatidylinositol (GPI)‐linked cell‐surface proteins as ligand‐binding components were required for Ret activation. Since GDNF and NTN are expected as therapeutic agents in neurodegenerative disorders such as Parkinson's disease and amyotrophic lateral sclerosis, the studies on the mechanisms of their biological actions through Ret would contribute to the development of new therapeutic strategies for these diseases.