The CARMA1-Bcl10 signaling complex selectively regulates JNK2 kinase in the T cell receptor-signaling pathway
The CARMA1-Bcl10 signaling complex selectively regulates JNK2 kinase in the T cell receptor-signaling pathway
复制标题
DOI：
10.1016/j.immuni.2006.11.008
复制
发表时间：
2007-01-01
期刊：
影响因子：
32.4
通讯作者：
Lin, Xin
中科院分区：
文献类型：
--
作者：
Blonska, Marzenna;Pappu, Bhanu P.;Lin, Xin
c-Jun NH 2-末端激酶（JNK）家族的成员在细胞活化、分化和凋亡中起关键作用。尽管许多研究表明JNK 1和JNK 2具有功能差异和冗余，但选择性激活JNK 1或JNK 2的上游信号通路仍然未知。在这项研究中，我们揭示了JNK激活的选择性机制，其中JNK 2，而不是JNK 1，在T细胞受体（TCR）刺激后由CARMA 1（一种支架分子）调节。JNK 2的这种CARMA 1依赖性调节通过支架分子Bcl 10起作用，Bcl 10与JNK 2诱导相关，并作为JNK相互作用蛋白（JIP）样支架组装激酶JNK 2，MKK 7和TAK 1。最后，我们发现CARMA 1和Bcl 10介导的JNK 2激活在调节c-Jun蛋白的量方面具有关键作用。总之，我们的研究提供了遗传学证据，即JNK 1和JNK 2在TCR信号通路中受到差异调节，并发挥不同的功能。
Members of the c-Jun NH2-terminal kinase (JNK) family play crucial roles in cell activation, differentiation, and apoptosis. Although many studies have indicated that JNK1 and JNK2 have functional differences and redundancy, the upstream signaling pathway that selectively activates JNK1 or JNK2 remains unknown. In this study, we have revealed a selective mechanism of JNK activation, in which JNK2, but not JNK1, was regulated by CARMA1, a scaffold molecule, after stimulation of the T cell receptor (TCR). This CARMA1-dependent regulation of JNK2 worked through the scaffold molecule Bcl10, which was inducibly associated with JNK2 and served as a JNK-interacting protein (JIP)-like scaffold to assemble the kinases JNK2, MKK7, and TAK1. Finally, we showed that CARMA1- and Bcl10-mediated JNK2 activation had a critical role in regulating the amount of c-Jun protein. Together, our studies provide genetic evidence that JNK1 and JNK2 are differentially regulated in the TCR-signaling pathway and play different functions.