Regulation of development and cancer by the R2B subfamily of RPTPs and the implications of proteolysis.
Regulation of development and cancer by the R2B subfamily of RPTPs and the implications of proteolysis.
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DOI：
10.1016/j.semcdb.2014.09.004
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发表时间：
2015-01
影响因子：
7.3
通讯作者：
Brady-Kalnay SM
中科院分区：
文献类型：
--
作者：
Craig SE;Brady-Kalnay SM
受体蛋白酪氨酸磷酸酶（RPTPs）的最初克隆是令人兴奋的，因为他们的假设功能，在平衡受体酪氨酸激酶信号。近年来，具有嗜同性细胞-细胞粘附能力的RPTP亚家族的成员，称为R2 B亚家族，已被证明具有超出抵消酪氨酸激酶活性的功能，通过独立影响细胞信号传导和调节细胞粘附。R2 B亚家族由四个成员组成：PTPmu（PTPRM）、PTPrho（PTPRT）、PTPkappa（PTP 3）和PCP-2（PTPRU）。RPTP的这个小的亚家族的影响是深远的，影响几个发育过程和癌症。事实上，R2 B RPTP被预测为肿瘤抑制剂，并且是癌症中最常见的突变蛋白酪氨酸磷酸酶（PTP）之一。混淆这些结论的是最近的研究，表明全长R2 B RPTP的蛋白水解导致致癌的细胞外和细胞内蛋白片段。本文综述了R2 B RPTP在发育和癌症中的作用，特别详细的机制和影响，蛋白水解对R2 B RPTP功能的现有知识。我们还触及的概念，利用R2 B蛋白水解开发癌症成像工具，并考虑R2 B蛋白水解的轴突导向，神经周围的入侵和集体细胞迁移的影响。
The initial cloning of receptor protein tyrosine phosphatases (RPTPs) was met with excitement because of their hypothesized function in counterbalancing receptor tyrosine kinase signaling. In recent years, members of a subfamily of RPTPs with homophilic cell-cell adhesion capabilities, known as the R2B subfamily, have been shown to have functions beyond that of counteracting tyrosine kinase activity, by independently influencing cell signaling in their own right and by regulating cell adhesion. The R2B subfamily is composed of four members: PTPmu (PTPRM), PTPrho (PTPRT), PTPkappa (PTPRK), and PCP-2 (PTPRU). The effects of this small subfamily of RPTPs is far reaching, influencing several developmental processes and cancer. In fact, R2B RPTPs are predicted to be tumor suppressors and are among the most frequently mutated protein tyrosine phosphatases (PTPs) in cancer. Confounding these conclusions are more recent studies suggesting that proteolysis of the full-length R2B RPTPs result in oncogenic extracellular and intracellular protein fragments. This review discusses the current knowledge of the role of R2B RPTPs in development and cancer, with special detail given to the mechanisms and implications that proteolysis has on R2B RPTP function. We also touch upon the concept of exploiting R2B proteolysis to develop cancer imaging tools, and consider the effects of R2B proteolysis on axon guidance, perineural invasion and collective cell migration.
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影响因子：
2.9
作者：
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