Mol Cell Biol. 2006 Jul;26(14):5497-508.

Ca2+/calmodulin-dependent protein kinase II is a modulator of CARMA1-mediated NF-kappaB activation.External

Ishiguro, K., Green, T., Rapley, J., Wachtel, H., Giallourakis, C., Landry, A., Cao, Z., Lu, N., Takafumi, A., Goto, H., Daly, M. J., Xavier, R. J.,
--- - Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
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.
PMID: 16809782External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
CARD Bcl-10 Link CARD11 Co-immunoprecipitation HEK293 Mouse Not specified Human 1-470 16809782
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Characterization
  Stoichiometry Affinity Protein-Protein interface Reference
Family DD1 DD2 Method Mutation Complex structure
CARD Bcl-10 Link CARD11 Co-immunoprecipitation S109A (CARD11) 16809782
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Functional Role
Family DD1 DD2 Method Death-related Death-unrelated Reference
CARD Bcl-10 Link CARD11 Luciferase assay NF-kB activation (Signalosome) 16809782
(Link: click this icon to show interactions only between the two corresponding DDs)