TY - JOUR
T1 - The GDNF/RET signaling pathway and human diseases
AU - Takahashi, Masahide
N1 - Funding Information:
I would like to thank members of my laboratory for their excellent contributions to the work presented in this review. This study was supported in part by a grant-in-aid for COE (Center of Excellence) research from the Ministry of Education, Science, Sports and Culture of Japan.
PY - 2001
Y1 - 2001
N2 - Glial cell line-derived neurotrophic factor (GDNF) and related molecules, neurturin, artemin and persephin, signal through a unique multicomponent receptor system consisting of RET tyrosine kinase and glycosyl-phosphatidylinositol-anchored coreceptor (GFRα1-4). These neurotrophic factors promote the survival of various neurons including peripheral autonomic and sensory neurons as well as central motor and dopamine neurons, and have been expected as therapeutic agents for neurodegenerative diseases. In addition, it turned out that the GDNF/RET signaling plays a crucial role in renal development and regulation of spermatogonia differentiation. RET mutations cause several human diseases such as papillary thyroid carcinoma, multiple endocrine neoplasia types 2A and 2B, and Hirschsprung's disease. The mutations resulted in RET activation or inactivation by various mechanisms and the biological properties of mutant proteins appeared to be correlated with disease phenotypes. The signaling pathways activated by GDNF or mutant RET are being extensively investigated to understand the molecular mechanisms of disease development and the physiological roles of the GDNF family ligands.
AB - Glial cell line-derived neurotrophic factor (GDNF) and related molecules, neurturin, artemin and persephin, signal through a unique multicomponent receptor system consisting of RET tyrosine kinase and glycosyl-phosphatidylinositol-anchored coreceptor (GFRα1-4). These neurotrophic factors promote the survival of various neurons including peripheral autonomic and sensory neurons as well as central motor and dopamine neurons, and have been expected as therapeutic agents for neurodegenerative diseases. In addition, it turned out that the GDNF/RET signaling plays a crucial role in renal development and regulation of spermatogonia differentiation. RET mutations cause several human diseases such as papillary thyroid carcinoma, multiple endocrine neoplasia types 2A and 2B, and Hirschsprung's disease. The mutations resulted in RET activation or inactivation by various mechanisms and the biological properties of mutant proteins appeared to be correlated with disease phenotypes. The signaling pathways activated by GDNF or mutant RET are being extensively investigated to understand the molecular mechanisms of disease development and the physiological roles of the GDNF family ligands.
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U2 - 10.1016/S1359-6101(01)00012-0
DO - 10.1016/S1359-6101(01)00012-0
M3 - Review article
C2 - 11544105
AN - SCOPUS:0034849573
SN - 1359-6101
VL - 12
SP - 361
EP - 373
JO - Cytokine and Growth Factor Reviews
JF - Cytokine and Growth Factor Reviews
IS - 4
ER -
