Regulation of innate immune response by MAP kinase phosphatase-1.
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.
Wang
Xianxi
X
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.
Liu
Yusen
Y
D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis; D054638:Dual Specificity Phosphatase 1; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000378:metabolism*; D007113:Immunity, Innate / Q000276:immunology*; D007155:Immunologic Factors / Q000378:metabolism; D007249:Inflammation / Q000382:microbiology; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000378:metabolism*; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism*
D018797:Cell Cycle Proteins; D016207:Cytokines; D017874:Immediate-Early Proteins; D007155:Immunologic Factors; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; D017027:Protein Tyrosine Phosphatases