The GDNF/RET signaling pathway and human diseases

被引：357

作者：

Takahashi, M ^{[1
]}

机构：

[1] Nagoya Univ, Grad Sch Med, Dept Pathol, Showa Ku, Nagoya, Aichi 4668550, Japan

来源：

CYTOKINE & GROWTH FACTOR REVIEWS | 2001年 / 12卷 / 04期

关键词：

RET proto-oncogene; glial cell line-derived neurotrophic factor; papillary thyroid carcinoma; multiple endocrine neoplasia 2; Hirschsprung's disease;

D O I：

10.1016/S1359-6101(01)00012-0

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 (GFR alpha1-4). 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. (C) 2001 Elsevier Science Ltd, All rights reserved.

引用

页码：361 / 373

页数：13

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