The MAGUK family protein CARD11 is essential for lymphocyte activation

Hiromitsu Hara, Teiji Wada, Chris Bakal, Ivona Kozieradzki, Shinobu Suzuki, Nobutaka Suzuki, Mai Nghiem, Emily K Griffiths, Connie Krawczyk, Birgit Bauer, Fulvio D'Acquisto, Sankar Ghosh, Wen Chen Yeh, Gottfried Baier, Robert Rottapel, Josef M Penninger

Research output: Contribution to journalArticlepeer-review

Abstract

Members of the MAGUK family proteins cluster receptors and intracellular signaling molecules at the neuronal synapse. We report that genetic inactivation of the MAGUK family protein CARD11/Carma1/Bimp3 results in a complete block in T and B cell immunity. CARD11 is essential for antigen receptor- and PKC-mediated proliferation and cytokine production in T and B cells due to a selective defect in JNK and NFkappaB activation. Moreover, B cell proliferation and JNK activation were impaired upon stimulation of TLR4 with lipopolysaccharide, indicating that CARD11 is involved in both the innate and adaptive immune systems. Our results show that the same family of molecules are critical regulators of neuronal synapses and immune receptor signaling.

Original languageEnglish
Pages (from-to)763-75
Number of pages13
JournalInfection and immunity
Volume18
Issue number6
Publication statusPublished - Jun 2003

Keywords

  • Animals
  • Apoptosis Regulatory Proteins
  • CARD Signaling Adaptor Proteins
  • Guanylate Cyclase
  • I-kappa B Proteins
  • JNK Mitogen-Activated Protein Kinases
  • Killer Cells, Natural
  • Lymphocyte Activation
  • Membrane Glycoproteins
  • Membrane Proteins
  • Mice
  • Mitogen-Activated Protein Kinases
  • Mutation
  • Protein Kinase C
  • Receptors, Antigen
  • Receptors, Cell Surface
  • Signal Transduction
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Journal Article

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