Phosphorylation of CARMA1 plays a critical role in T cell receptor-mediated NF-κB activation

Reiko Matsumoto, Donghai Wang, Marzenna Blonska, Hongxiu Li, Masayuki Kobayashi, Bhanu Pappu, Yuhong Chen, Demin Wang, Xin Lin

Research output: Contribution to journalArticle

200 Scopus citations

Abstract

CARMA1 mediates T cell receptor (TCR)-induced NF-κB activation. However, how TCR links to CARMA1 in the signaling pathway is not clear. Here, we show that CARMA1 is inducibly phosphorylated after TCR-CD28 costimulation. This phosphorylation is likely induced by PKCθ, since PKCθ induces phosphorylation of CARMA1 in vitro and in vivo. Our results indicate that the PKCθ-induced phosphorylation of CARMA1 likely occurs on Ser552 on the Linker region of CARMA1. Importantly, expression of CARMA1 mutant, in which Ser552 is mutated, fails to mediate TCR-induced NF-κB activation in CARMA1-deficient T cells. The functional defect of this CARMA1 mutant is likely due to the fact that this mutant cannot be phosphorylated at the critical residue, thereby failing to recruit the downstream signaling components into the immunological synapse. Together, our studies provide the first genetic evidence that the phosphorylation of CARMA1 plays a critical role in the TCR signaling pathway.

Original languageEnglish (US)
Pages (from-to)575-585
Number of pages11
JournalImmunity
Volume23
Issue number6
DOIs
StatePublished - Dec 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Matsumoto, R., Wang, D., Blonska, M., Li, H., Kobayashi, M., Pappu, B., Chen, Y., Wang, D., & Lin, X. (2005). Phosphorylation of CARMA1 plays a critical role in T cell receptor-mediated NF-κB activation. Immunity, 23(6), 575-585. https://doi.org/10.1016/j.immuni.2005.10.007