Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, BBSRB, 741S. Limestone St., Lexington, KY 40536-0509, USA.
Cell Signal. 2013 Oct;25(10):2060-8. doi: 10.1016/j.cellsig.2013.06.002. Epub 2013 Jun 11.
Ras family small GTPases serve as binary molecular switches to regulate a broad array of cellular signaling cascades, playing essential roles in a vast range of normal physiological processes, with dysregulation of numerous Ras-superfamily G-protein-dependent regulatory cascades underlying the development of human disease. However, the physiological function for many "orphan" Ras-related GTPases remain poorly characterized, including members of the Rit subfamily GTPases. Rit is the founding member of a novel branch of the Ras subfamily, sharing close homology with the neuronally expressed Rin and Drosophila Ric GTPases. Here, we highlight recent studies using transgenic and knockout animal models which have begun to elucidate the physiological roles for the Rit subfamily, including emerging roles in the regulation of neuronal morphology and cellular survival signaling, and discuss new genetic data implicating Rit and Rin signaling in disorders such as cancer, Parkinson's disease, autism, and schizophrenia.
Ras 家族小 GTP 酶作为双分子分子开关，调节广泛的细胞信号级联反应，在大量正常生理过程中发挥着重要作用，许多 Ras 超家族 G 蛋白依赖性调节级联反应的失调是人类疾病发展的基础。然而，许多“孤儿” Ras 相关 GTP 酶的生理功能仍未得到充分描述，包括 Rit 亚家族 GTP 酶的成员。Rit 是 Ras 亚家族的一个新分支的创始成员，与神经元表达的 Rin 和果蝇 Ric GTP 酶具有密切的同源性。在这里，我们强调了最近使用转基因和基因敲除动物模型的研究，这些研究开始阐明 Rit 亚家族的生理作用，包括在调节神经元形态和细胞存活信号中的新作用，并讨论了新的遗传数据表明 Rit 和 Rin 信号在癌症、帕金森病、自闭症和精神分裂症等疾病中的作用。
