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Regulation of c‐Jun N terminal kinase (JNK) signaling by dual specificity phosphatases (DUSPs) in adipocytes during inflammatory stress
Author(s) -
Ferguson Bradley Scott,
Nam Heesun,
Hopkins Robin G,
Morrison Ron F
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.910.12
Subject(s) - microbiology and biotechnology , kinase , phosphatase , inflammation , signal transduction , dual specificity phosphatase , insulin resistance , tumor necrosis factor alpha , biology , phosphorylation , endocrinology , immunology , diabetes mellitus
Chronic inflammation is an important element of pathogenic mechanisms linking obesity to diabetes. Mounting evidence strongly suggests that the JNK signaling pathway plays a central role in mediating the inflammatory process as mice deficient in JNK activity are protected against diet‐induced or genetic models of insulin resistance. While numerous studies have examined the upstream signaling on JNK activation, few have addressed the role of JNK deactivation and its effect on biological outcome. Evidence now indicates a critical role for DUSPs in the deactivation of JNK and other signaling pathways. Using 3T3‐L1 adipocytes stimulated with tumor necrosis factor α (TNFα) as a model of inflammation, we examined the role of DUSPs on JNK deactivation and inflammatory function. We show that the transient activation (<1h) of JNK signaling in response to TNFα is prolonged (>2h) in the presence of transcriptional inhibition with actinomyosin D suggesting a role for inducible phosphatases. Based on these data, we identified DUSPs expressed in preadipocytes and show that dusp1, dusp8, and dusp16 are induced in response to TNFα. Of these, dusp8 and dusp16 are regulated by JNK in a negative feedback manner. Focus on kinase‐phosphatase relationships will increase our knowledge governing the inflammatory process that couples obesity to insulin resistance. Supported by NIH (5R21DK072067‐02). Grant Funding Source NIH 5R21DK072067‐02