Faculty Collaboration Database

The CARMA1-Bcl10 signaling complex selectively regulates JNK2 kinase in the T cell receptor-signaling pathway. Immunity 2007 Jan;26(1):55-66

Date

12/27/2006

Pubmed ID

17189706

Pubmed Central ID

PMC1802095

DOI

10.1016/j.immuni.2006.11.008

Scopus ID

2-s2.0-33846235557 (requires institutional sign-in at Scopus site)   83 Citations

Abstract

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.

Author List

Blonska M, Pappu BP, Matsumoto R, Li H, Su B, Wang D, Lin X

Author

Demin Wang PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis Regulatory Proteins
Blotting, Western
CARD Signaling Adaptor Proteins
Enzyme Activation
Enzyme-Linked Immunosorbent Assay
Guanylate Cyclase
Humans
Jurkat Cells
Mice
Mitogen-Activated Protein Kinase 9
Receptors, Antigen, T-Cell
Signal Transduction