A loss-of-function mutation of c-kit results in depletion of mast cells and interstitial cells of Cajal, while its gain-of-function mutation results in their oncogenesis
A loss-of-function mutation of c-kit results in depletion of mast cells and interstitial cells of Cajal, while its gain-of-function mutation results in their oncogenesis
复制标题
DOI：
10.1016/s0027-5107(01)00117-8
复制
发表时间：
2001-06-02
影响因子：
2.3
通讯作者：
Nishida, T
中科院分区：
文献类型：
--
作者：
Kitamura, Y;Hirota, S;Nishida, T
c-kit受体酪氨酸激酶（KIT）的功能缺失突变导致肥大细胞和Cajal间质细胞（ICC）耗竭。相反，KIT的功能获得性突变诱导肥大细胞和ICC的肿瘤。在人类中，肥大细胞肿瘤和ICC之间的突变位点是不同的。前者位于跨膜区和酪氨酸激酶区之间，后者位于酪氨酸激酶区。此外，组成性激活的机制是不同的。点突变和/或缺失的质膜结构域诱导的KIT二聚体，和二聚化的KIT被激活。酪氨酸激酶结构域中特定天冬氨酸的点突变诱导自发活化而不形成二聚体。c-kit基因的突变是了解人类和小鼠突变与疾病之间关系的良好模型。(C)2001爱思唯尔科技有限公司。保留所有权利。
Loss-of-function mutations of the c-kit receptor tyrosine kinase (KIT) result in depletion of mast cells and interstitial cells of Cajal (ICCs). In contrast, gain-of-function mutations of KIT induce neoplasms of mast cells and ICCs. In humans, the sites of mutations are different between mast cell neoplasms and those of ICCs. The former were found in the juxtamembrane domain between the transmembrane and tyrosine kinase domains, and the latter in the tyrosine kinase domain. Moreover, the mechanism of constitutive activation is different. Point mutations and/or deletions in the juxtamembrane domain induced the KIT dimerization, and the dimerized KIT was activated. A point mutation at the particular aspartic acid in the tyrosine kinase domain induced spontaneous activation without forming dimers. Mutations of the c-kit gene are a good model for understanding the relationship between mutations and diseases in both humans and mice. (C) 2001 Elsevier Science B.V. All rights reserved.