Wang Xianxi, Liu Yusen
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.
Cell Signal. 2007 Jul;19(7):1372-82. doi: 10.1016/j.cellsig.2007.03.013. Epub 2007 Apr 20.
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.
丝裂原活化蛋白（MAP）激酶级联反应是在促炎细胞因子生物合成中起关键调节作用的信号转导途径。MAP激酶磷酸酶（MKP）-1是MKP家族的典型成员，对于MAP激酶p38和JNK的去磷酸化/失活至关重要。早期使用培养的永生化巨噬细胞进行的研究提供了令人信服的证据，表明MKP-1使p38和JNK失活，从而限制了暴露于微生物成分的先天免疫细胞中促炎细胞因子的生物合成。最近使用MKP-1基因敲除小鼠进行的研究证实了MKP-1在p38和JNK活性的反馈控制中的核心功能，以及MKP-1作为体内促炎细胞因子合成的负调节剂的关键生理功能。MKP-1被证明是先天免疫反应的主要反馈调节因子，并且在预防病原体感染期间的败血症性休克和多器官功能障碍中起关键作用。在这篇综述中，我们将更新关于MKP-1的生化特性和调节的研究，并总结我们对这种关键磷酸酶在先天免疫反应中的生理功能的理解。
