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Cell Signal. 2007 Jul;19(7):1372-82. Epub 2007 Apr 20.

Regulation of innate immune response by MAP kinase phosphatase-1.

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Center for Perinatal Research, Children's Research Institute, Columbus Children's Hospital, Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA.


Mitogen-activated protein (MAP) kinase cascades are signal transduction pathways that play pivotal regulatory roles in the biosynthesis of pro-inflammatory cytokines. MAP kinase phosphatase (MKP)-1, an archetypal member of the MKP family, is essential for the dephosphorylation/deactivation of MAP kinases p38 and JNK. Earlier studies conducted using cultured immortalized macrophages provided compelling evidence indicating that MKP-1 deactivates p38 and JNK, thereby limiting pro-inflammatory cytokine biosynthesis in innate immune cells exposed to microbial components. Recent studies employing MKP-1 knockout mice have confirmed the central function of MKP-1 in the feedback control of p38 and JNK activity as well as the crucial physiological function of MKP-1 as a negative regulator of the synthesis of pro-inflammatory cytokines in vivo. MKP-1 was shown to be a major feedback regulator of the innate immune response and to play a critical role in preventing septic shock and multi-organ dysfunction during pathogenic infection. In this review, we will update the studies on the biochemical properties and the regulation of MKP-1, and summarize our understanding on the physiological function of this key phosphatase in the innate immune response.

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