J Biol Chem. 2004 Jan 9;279(2):1570-4. Epub 2003 Nov 24.

Rip2 participates in Bcl10 signaling and T-cell receptor-mediated NF-kappaB activation.External

Ruefli-Brasse, A. A., Lee, W. P., Hurst, S., Dixit, V. M.,
--- - Department of Molecular Oncology, Genentech, Inc., South San Francisco, California 94080, USA.
Engagement of the T-cell receptor (TCR) initiates a signaling cascade that ultimately results in activation of the transcription factor NF-kappaB, which regulates many T-cell functions including proliferation, differentiation and cytokine production. Herein we demonstrate that Rip2, a caspase recruitment domain (CARD)-containing serine/threonine kinase, plays an important role in this cascade and is required for optimal TCR signaling and NF-kappaB activation. Following TCR engagement, Rip2 associated with Bcl10, a CARD-containing signaling component of the TCR-induced NF-kappaB pathway, and induced its phosphorylation. Rip2-deficient mice were defective in TCR-induced NF-kappaB activation, interleukin-2 production, and proliferation in vitro and exhibited defective T-cell-dependent responses in vivo. The defect in Rip2-/- T-cells correlated with a lack of TCR-induced Bcl10 phosphorylation. Furthermore, deficiency in Bcl10-dependent NF-kappaB activation could be rescued in Rip2-/- embryonic fibroblasts by exogenous wild-type Rip2 but not a kinase-dead mutant. Together these data define an important role for Rip2 in TCR-induced NF-kappaB activation and T-cell function and highlight the significance of post-translational modification of Bcl10 by Rip2 in T-cell signaling.
PMID: 14638696External
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 Bcl-10 Co-immunoprecipitation HEK293 Not specified Full length Human Full length 14638696
CARD Bcl-10 Link RIPK2 Co-immunoprecipitation HEK293 Human Full length Not specified Full length 14638696
CARD Bcl-10 Link RIPK2 Co-immunoprecipitation HEK293 Not specified Full length Human Full length 14638696
(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 RIPK2 Luciferase assay NF-kB activation 14638696
(Link: click this icon to show interactions only between the two corresponding DDs)