Nat Immunol. 2007 Jun;8(6):619-29. Epub 2007 May 7.

The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors.External

Hara, H., Ishihara, C., Takeuchi, A., Imanishi, T., Xue, L., Morris, S. W., Inui, M., Takai, T., Shibuya, A., Saijo, S., Iwakura, Y., Ohno, N., Koseki, H., Yoshida, H., Penninger, J. M., Saito, T.,
--- - Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan. harah@cc.saga-u.ac.jp
Immunoreceptor tyrosine-based activation motifs (ITAMs) are crucial in antigen receptor signaling in acquired immunity. Although receptors associated with the ITAM-bearing adaptors FcRgamma and DAP12 on myeloid cells have been suggested to activate innate immune responses, the mechanism coupling those receptors to 'downstream' signaling events is unclear. The CARMA1-Bcl-10-MALT1 complex is critical for the activation of transcription factor NF-kappaB in lymphocytes but has an unclear function in myeloid cells. Here we report that deletion of the gene encoding the Bcl-10 adaptor-binding partner CARD9 resulted in impaired myeloid cell activation of NF-kappaB signaling by several ITAM-associated receptors. Moreover, CARD9 was required for Toll-like receptor-induced activation of dendritic cells through the activation of mitogen-activated protein kinases. Although Bcl10-/- and Card9-/- mice had similar signaling impairment in myeloid cells, Card11-/- (CARMA1-deficient) myeloid cell responses were normal, and although Card11-/- lymphocytes were defective in antigen receptor-mediated activation, Card9-/- lymphocytes were not. Thus, the activation of lymphoid and myeloid cells through ITAM-associated receptors or Toll-like receptors is regulated by CARMA1-Bcl-10 and CARD9-Bcl-10, respectively.
PMID: 17486093External
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 CARD9 Link RIPK2 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 17486093
(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 CARD9 Link RIPK2 Western blotting Bcl-10 phosphorylation increase 17486093
(Link: click this icon to show interactions only between the two corresponding DDs)