MEKK3 is required for lysophosphatidic acid-induced NF-κB activation |
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| Authors: | Wenjing Sun Hongxiu Li Yang Yu Yihui Fan Brian C. Grabiner Renfang Mao Ningling Ge Hong Zhang Songbin Fu Xin Lin Jianhua Yang |
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| Affiliation: | aTexas Children's Cancer Center, Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, United States;bLaboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China;cDepartment of Molecular and Cellular Oncology, the University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, United States;dDepartment of Pathology, Baylor College of Medicine, Houston, TX 77030, United States |
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| 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-κB activation by acting on its GPCR receptor, the molecular mechanism of LPA receptor-mediated NF-κB activation remains to be well defined. In the present study, by using MEKK3-, TAK1-, and IKKβ-deficient murine embryonic fibroblasts (MEFs), we found that MEKK3 but not TAK1 deficiency impairs LPA and protein kinase C (PKC)-induced IκB kinase (IKK)-NF-κB activation, and IKKβ is required for PKC-induced NF-κB 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-κB activation. |
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| Keywords: | NF-κ B LPA GPCR MEKK3 TAK1 |
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