The CARMA1-Bcl10 complex selectively regulates JNK2 in the T cell receptor signaling pathway

Members of the c-Jun NH 2 -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 novel regulatory mechanism of JNK activation, in which JNK2, but not JNK1, is regulated by CARMA1, a scaffold molecule, following stimulation of the T cell receptor (TCR). This CARMA1-dependent regulation of JNK2 is through Bcl10 that inducibly associates with JNK2 and serves as a JNK-interacting protein (JIP)-like scaffold to assemble JNK2, MKK7, and TAK1. Finally, we show that CARMA1- and Bcl10-mediated JNK2 activation plays a critical role in regulating the level of c-Jun protein. Together, our studies provide the first genetic evidence that JNK1 and JNK2 are differentially regulated in the TCR signaling pathway, and play different functions.