The CARMA1-Bcl10 signaling complex selectively regulates JNK2 kinase 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 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.
Blonska
Marzenna
M
Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Pappu
Bhanu P
BP
Matsumoto
Reiko
R
Li
Hongxiu
H
Su
Bing
B
Wang
Demin
D
Lin
Xin
X
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D053468:CARD Signaling Adaptor Proteins / Q000276:immunology / Q000378:metabolism*; D004789:Enzyme Activation / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006162:Guanylate Cyclase / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D048056:Mitogen-Activated Protein Kinase 9 / Q000276:immunology / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*
D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D011948:Receptors, Antigen, T-Cell; D048056:Mitogen-Activated Protein Kinase 9; C426242:CARD11 protein, human; D006162:Guanylate Cyclase