Nitta Ryan T, Badal Shawn S, Wong Albert J
Department of Neurosurgery, Cancer Biology Program, Stanford University Medical Center, Stanford, California, USA.
Methods Enzymol. 2010;484:531-48. doi: 10.1016/B978-0-12-381298-8.00026-5.
The c-Jun N-terminal kinases (JNK) are important regulators of cell growth, proliferation, and apoptosis. JNKs are typically activated by a sequence of events that include phosphorylation of its T-P-Y motif by an upstream kinase, followed by homodimerization and translocation to the nucleus. Constitutive activation of JNK has been found in a variety of cancers including non-small cell lung carcinomas, gliomas, and mantle cell lymphoma. In vitro studies show that constitutive activation of JNK induces a transformed phenotype in fibroblasts and enhances tumorigenicity in a variety of cell lines. Interestingly, a subset of JNK isoforms was recently found to autoactivate rendering the proteins constitutively active. These constitutively active JNK proteins were found to play a pivotal role in activating transcription factors that increase cellular growth and tumor formation in mice. In this chapter, we describe techniques and methods that have been successfully used to study the three components of JNK activation. Use of these techniques may lead to a better understanding of the components of JNK pathways and how JNK is activated in cancer cells.
c-Jun氨基末端激酶（JNK）是细胞生长、增殖和凋亡的重要调节因子。JNK通常通过一系列事件被激活，这些事件包括上游激酶对其T-P-Y基序的磷酸化，随后是同二聚化并转位至细胞核。JNK的组成型激活已在多种癌症中被发现，包括非小细胞肺癌、神经胶质瘤和套细胞淋巴瘤。体外研究表明，JNK的组成型激活可诱导成纤维细胞出现转化表型，并增强多种细胞系的致瘤性。有趣的是，最近发现一部分JNK亚型可自我激活，使这些蛋白处于组成型激活状态。这些组成型激活的JNK蛋白在激活增加小鼠细胞生长和肿瘤形成的转录因子方面起着关键作用。在本章中，我们描述了已成功用于研究JNK激活的三个组成部分的技术和方法。使用这些技术可能有助于更好地理解JNK信号通路的组成部分以及JNK在癌细胞中是如何被激活的。
