Molecular and Cellular Biology · 2006 · 102 citations · 47 references
Life SciencesImmunologyMolecular BiologyCell SignalingCellular ImmunologySignal TransductionImmune Cell SignalingImmune SignalingImmune SynapseProtein Kinase CascadesT Cell ActivationT Cell Receptor SignalingCalcium-calmodulin SignalingCalcium-dependent Protein Kinase IiCalmodulin-dependent Protein Kinase IiCalmodulin-mediated RegulationCell ActivationImmune Synapse SignalingNf-κb SignalingT Cell Activation Modulation
CARMA1 is a central regulator of NF-kappaB activation in lymphocytes. CARMA1 and Bcl10 functionally interact and control NF-kappaB signaling downstream of the T-cell receptor (TCR). Computational analysis of expression neighborhoods of CARMA1-Bcl10MALT 1 for enrichment in kinases identified calmodulin-dependent protein kinase II (CaMKII) as an important component of this pathway. Here we report that Ca(2+)/CaMKII is redistributed to the immune synapse following T-cell activation and that CaMKII is critical for NF-kappaB activation induced by TCR stimulation. Furthermore, CaMKII enhances CARMA1-induced NF-kappaB activation. Moreover, we have shown that CaMKII phosphorylates CARMA1 on Ser109 and that the phosphorylation facilitates the interaction between CARMA1 and Bcl10. These results provide a novel function for CaMKII in TCR signaling and CARMA1-induced NF-kappaB activation.
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A Gene-Coexpression Network for Global Discovery of Conserved Genetic Modules
Joshua M. Stuart, Eran Segal, Daphne Koller et al. · Science · 2003 · 2.4K citations