| First Author | Klemm S | Year | 2007 |
| Journal | Proc Natl Acad Sci U S A | Volume | 104 |
| Issue | 1 | Pages | 134-8 |
| PubMed ID | 17095601 | Mgi Jnum | J:118745 |
| Mgi Id | MGI:3700322 | Doi | 10.1073/pnas.0608388103 |
| Citation | Klemm S, et al. (2007) Bcl10 and Malt1 control lysophosphatidic acid-induced NF-kappaB activation and cytokine production. Proc Natl Acad Sci U S A 104(1):134-8 |
| abstractText | 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-kappaB activation. Both proteins were previously known to activate NF-kappaB 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 IkappaB-alpha and the subsequent NF-kappaB induction in response to LPA stimulation. Bcl10 and Malt1 cooperate with PKCs selectively for LPA-induced NF-kappaB 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-kappaB-inducing signaling pathway downstream of GPCRs and reveal previously unrecognized functions for Bcl10/Malt1 signaling in nonimmune cells. |
