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Cell Signal. 2009 Oct;21(10):1488-94. doi: 10.1016/j.cellsig.2009.05.007. Epub 2009 May 22.

MEKK3 is required for lysophosphatidic acid-induced NF-kappaB activation.

Author information

1
Texas Children's Cancer Center, Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.

Abstract

Lysophosphatidic acid (LPA) is a potent agonist that exerts various cellular functions on many cell types through binding to its cognate G protein-coupled receptors (GPCRs). Although LPA induces NF-kappaB activation by acting on its GPCR receptor, the molecular mechanism of LPA receptor-mediated NF-kappaB activation remains to be well defined. In the present study, by using MEKK3-, TAK1-, and IKKbeta-deficient murine embryonic fibroblasts (MEFs), we found that MEKK3 but not TAK1 deficiency impairs LPA and protein kinase C (PKC)-induced IkappaB kinase (IKK)-NF-kappaB activation, and IKKbeta is required for PKC-induced NF-kappaB activation. In addition, we demonstrate that LPA and PKC-induced IL-6 and MIP-2 production are abolished in the absence of MEKK3 but not TAK1. Together, our results provide the genetic evidence that MEKK3 but not TAK1 is required for LPA receptor-mediated IKK-NF-kappaB activation.

PMID:
19465115
PMCID:
PMC2719299
DOI:
10.1016/j.cellsig.2009.05.007
[Indexed for MEDLINE]
Free PMC Article

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