JHIBRG:Abstract Apr 19 2007

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Regulation of MAP Kinase Phosphatase-1 and Inflammation

MAP kinase signaling pathway is one of the major signal transduction pathway that mediates various extracellular signals such as hormones, growth factors, cytokines, and microbial antigens. MAP kinase signaling transduces the activation signal through phosphorylation relay from upper level kinases to downstream kinases. p38, ERK, and JNK MAP kinases are especially essential regulators in immune responses including LPS-induced TLR4 signaling. Inactivation of MAP kinase signaling is primarily achieved by a group of MAP kinase phosphatases (MKPs). MKPs negatively regulate MAP kinases by dephosphorylating p38, ERK, and JNK MAP kinases. Especially, MKP-1 is the archtype of MKP family and an essential endogenous negative regulator of innate immune responses. In our experiment, we could modify MKP-1 and modulate LPS-induced phosphorylation of MAP kinases. Our results suggest that MKP-1 is a potential therapeutic target in sepsis.

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