Li Ying-Hua, Zhong Shan, Rong Zhi-Li, Ren Yong-Ming, Li Zhi-Yong, Zhang Shu-Ping, Chang Zhijie, Liu Li
Tsinghua Institute of Genome Research, Institute of Biomedicine & School of Medicine, Tsinghua University, Beijing 100084, China.
Biochem Biophys Res Commun. 2007 May 4;356(2):444-9. doi: 10.1016/j.bbrc.2007.02.154. Epub 2007 Mar 8.
Receptor protein tyrosine kinases (RPTKs) are essential mediators of cell growth, differentiation, migration, and metabolism. Recently, a novel RPTK named NOK has been cloned and characterized. In current study, we investigated the role of the carboxyl terminal tyrosine 417 residue of NOK in the activations of different signaling pathways. A single tyrosine to phenylalanine point mutation at Y417 site (Y417F) not only dramatically enhanced the NOK-induced activation of extracellular signal-regulated kinase (ERK), but also markedly promoted the NOK-mediated activation of both signal transducer and activator of transcription 1 and 3 (STAT1 and 3). Moreover, the proliferation potential of NIH3T3-NOK (Y417F) stable cells were significantly elevated as compared with that of NIH3T3-NOK. Overall, our results demonstrate that the tyrosine Y417 residue at the carboxyl tail of NOK exhibits an autoinhibitory role in NOK-mediated signaling transductions.
受体蛋白酪氨酸激酶（RPTKs）是细胞生长、分化、迁移和代谢的重要介质。最近，一种名为NOK的新型RPTK已被克隆和鉴定。在当前的研究中，我们研究了NOK羧基末端酪氨酸417残基在不同信号通路激活中的作用。Y417位点的单个酪氨酸到苯丙氨酸点突变（Y417F）不仅显著增强了NOK诱导的细胞外信号调节激酶（ERK）的激活，而且还显著促进了NOK介导的信号转导和转录激活因子1和3（STAT1和3）的激活。此外，与NIH3T3-NOK相比，NIH3T3-NOK（Y417F）稳定细胞的增殖潜力显著提高。总体而言，我们的结果表明，NOK羧基末端的酪氨酸Y417残基在NOK介导的信号转导中发挥自抑制作用。
