Pivotal Role of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 in Inflammatory Pulmonary Diseases.
Pivotal Role of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 in Inflammatory Pulmonary Diseases.
复制标题
丝裂原激活蛋白激酶激活蛋白激酶 2 在炎症性肺部疾病中的关键作用。
DOI：
10.2174/1389203716666150629121324
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发表时间：
2016
影响因子：
2.8
通讯作者：
Christman JW
中科院分区：
文献类型：
--
作者：
Qian F;Deng J;Wang G;Ye RD;Christman JW
丝裂原活化蛋白激酶（MAPK）活化蛋白激酶（MK2）在体内仅受p38 MAPK调节。在p38 MAPK活化后，MK2与p38 MAPK结合，导致TTP、Hsp 27、Akt和Cdc 25的磷酸化，所述TTP、Hsp 27、Akt和Cdc 25参与各种必需细胞功能的调节。本文综述了MK2在调节TNF-α产生、NADPH氧化酶活化、中性粒细胞迁移和DNA损伤诱导的细胞周期阻滞等方面的分子机制，这些机制参与了急性肺损伤、肺纤维化和非小细胞肺癌的分子发病机制。目前和新出现的信息表明，开发MK2抑制剂和阻断MK2介导的信号通路是治疗炎症和纤维化肺病和肺癌的潜在治疗策略。
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 is a potential therapeutic strategy for treatment of inflammatory and fibrotic lung diseases and lung cancer.