title: Pivotal Role of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 in Inflammatory Pulmonary Diseases.
abstract: Mitogen-activated protein kinase (MAPK)-activated protein kinase (MK2) is exclusively regulated by p38 MAPK in vivo. Upon activation of p38 MAPK, MK2 binds with p38 MAPK, leading to phosphorylation of TTP, Hsp27, Akt, and Cdc25 that are involved in regulation of various essential cellular functions. In this review, we discuss current knowledge about molecular mechanisms of MK2 in regulation of TNF-α production, NADPH oxidase activation, neutrophil migration, and DNA-damage-induced cell cycle arrest which are involved in the molecular pathogenesis of acute lung injury, pulmonary fibrosis, and non-small-cell lung cancer. Collectively current and emerging new information indicate that developing MK2 inhibitors and blocking MK2-mediated signal pathways are potential therapeutic strategies for treatment of inflammatory and fibrotic lung diseases and lung cancer.
authors.affiliation: Department of Internal Medicine, The Ohio State University, 201 Davis Heart and Lung Research Institute, 473 West 12th Avenue, Columbus, OH 43210, USA. fengqian7@outlook.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.forename: Jing
authors.initials: J
authors.lastname: Deng
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Richard D
authors.initials: RD
authors.lastname: Ye
authors.affiliation: Department of Internal Medicine, The Ohio State University, 201 Davis Heart and Lung Research Institute, 473 West 12th Avenue, Columbus, OH 43210, USA. john.christman@osumc.edu.
authors.forename: John W
authors.initials: JW
authors.lastname: Christman
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004249:DNA Damage; D006801:Humans; D007249:Inflammation / Q000150:complications; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008171:Lung Diseases / Q000150:complications / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D019255:NADPH Oxidases; D017346:Protein Serine-Threonine Kinases; D000099190:MAP-Kinase-Activated Kinase 2