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Intracellular RET signaling pathways activated by GDNF
Cell and Tissue Research ( IF 3.6 ) Pub Date : 2020-08-20 , DOI: 10.1007/s00441-020-03262-1
Kumi Kawai 1 , Masahide Takahashi 2, 3
Affiliation  

Activation of REarranged during Transfection (RET) proto-oncogene is responsible for various human cancers such as papillary and medullary thyroid carcinomas and non-small cell lung carcinomas. RET activation in these tumors is caused by point mutations or gene rearrangements, resulting in constitutive activation of RET tyrosine kinase. Physiologically, RET is activated by glial cell line–derived neurotrophic factor (GDNF) ligands that bind to coreceptor GDNF family receptor alphas (GFRαs), leading to RET dimerization. GDNF-GFRα1-RET signaling plays crucial roles in the development of the enteric nervous system, kidney and lower urinary tract as well as in spermatogenesis. Intracellular tyrosine phosphorylation in RET and recruitment of adaptor proteins to phosphotyrosines are essential for various biological functions. Significance of intracellular RET signaling pathways activated by GDNF is discussed and summarized in this review.

中文翻译:

GDNF 激活的细胞内 RET 信号通路

转染过程中重排 (RET) 原癌基因的激活是导致各种人类癌症的原因,例如甲状腺乳头状癌和髓样癌以及非小细胞肺癌。这些肿瘤中的 RET 激活是由点突变或基因重排引起的,导致 RET 酪氨酸激酶的组成型激活。在生理上,RET 被神经胶质细胞系衍生的神经营养因子 (GDNF) 配体激活,该配体与辅助受体 GDNF 家族受体α (GFRα) 结合,导致 RET 二聚化。GDNF-GFRα1-RET 信号传导在肠道神经系统、肾脏和下泌尿道的发育以及精子发生中起着至关重要的作用。RET 中的细胞内酪氨酸磷酸化和接头蛋白向磷酸酪氨酸的募集对于各种生物学功能至关重要。
更新日期:2020-08-20
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