Bcl10 and Malt1 control lysophosphatidic acid-induced NF-κB activation and cytokine production

Stefanie Klemm, Stephanie Zimmermann, Christian Peschel, Tak W. Mak, Jürgen Ruland

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


Lysophosphatidic acid (LPA) is a potent bioactive phospholipid that stimulates a variety of cellular responses by acting on cognate G protein-coupled receptors (GPCRs). There is increasing evidence that LPA signaling reprograms gene expression, but the GPCR-induced pathways connecting LPA receptor stimulation to downstream transcription factors are not well characterized. Here, we identify the adapter proteins Bcl10 and Malt1 as essential mediators of LPA-induced NF-κB activation. Both proteins were previously known to activate NF-κB in response to antigen receptor ligation on lymphocytes, but their functions in nonimmune cells are still largely undefined. By using murine embryonic fibroblasts from Bcl10- or Malt1-deficient mice as a genetic model, we report that Bcl10 and Malt1 are critically required for the degradation of IκB-α and the subsequent NF-κB induction in response to LPA stimulation. Bcl10 and Malt1 cooperate with PKCs selectively for LPA-induced NF-κB activation but are dispensable for the activation of the Jnk, p38, Erk MAP kinase, and Akt signaling pathways. In a biological readout, we demonstrate that LPA-induced IL-6 production is abolished in the absence of Bcl10. Thus, our results identify a NF-κB-inducing signaling pathway downstream of GPCRs and reveal previously unrecognized functions for Bcl10/Malt1 signaling in nonimmune cells.

Original languageEnglish
Pages (from-to)134-138
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number1
StatePublished - 2 Jan 2007
Externally publishedYes


  • G protein-coupled receptor
  • Signal transduction


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