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Pivotal Role of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 in Inflammatory Pulmonary Diseases

[ Vol. 17 , Issue. 4 ]

Author(s):

Feng Qian, Jing Deng, Gang Wang, Richard D. Ye and John W. Christman   Pages 332 - 342 ( 11 )

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.

Keywords:

Acute lung injury, inflammation, lung cancer, MK2, MAPK, pulmonary fibrosis.

Affiliation:

Department of Internal Medicine, The Ohio State University, 201 Davis Heart and Lung Research Institute, 473 West 12th Avenue, Columbus, OH 43210, USA.`



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