Jaeschke Anja, Karasarides Maria, Ventura Juan-Jose, Ehrhardt Anka, Zhang Chao, Flavell Richard A, Shokat Kevan M, Davis Roger J
Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Mol Cell. 2006 Sep 15;23(6):899-911. doi: 10.1016/j.molcel.2006.07.028.
The cJun NH(2)-terminal kinase (JNK) signal transduction pathway is established to be an important mechanism of regulation of the cJun transcription factor. Studies of Jnk1(-/-) and Jnk2(-/-) mice suggest that the JNK1 and JNK2 isoforms have opposite effects on cJun expression and proliferation. Here, we demonstrate, using a chemical genetic approach, that both JNK1 and JNK2 are positive regulators of these processes. We show that competition between JNK1 and JNK2 contributes to the opposite phenotypes caused by JNK1 and JNK2 deficiency. Our analysis illustrates the power of a chemical genetics approach for the analysis of signal transduction pathways and also highlights the limitations of single gene knockout strategies for the analysis of signaling pathways that are formed by a network of interacting proteins.
cJun氨基末端激酶（JNK）信号转导通路已被确认为是调控cJun转录因子的重要机制。对Jnk1(-/-)和Jnk2(-/-)小鼠的研究表明，JNK1和JNK2亚型对cJun表达和细胞增殖具有相反的作用。在此，我们运用化学遗传学方法证明，JNK1和JNK2都是这些过程的正向调节因子。我们表明，JNK1和JNK2之间的竞争导致了JNK1和JNK2缺陷所引起的相反表型。我们的分析阐明了化学遗传学方法在信号转导通路分析中的作用，同时也突出了单基因敲除策略在分析由相互作用蛋白网络形成的信号通路时的局限性。
