Bidirectional regulation of neutrophil migration by mitogen-activated protein kinases

被引：174

作者：

Liu, Xiaowen ^{[1
,2
]}

Ma, Bo ^{[3
]}

Malik, Asrar B. ^{[2
,4
]}

Tang, Haiyang ^{[1
,2
]}

Yang, Tao ^{[3
]}

Sun, Bo ^{[1
,2
,3
]}

Wang, Gang ^{[1
,2
]}

Minshall, Richard D. ^{[2
,5
]}

Li, Yan ^{[6
]}

Zhao, Yong ^{[3
]}

Ye, Richard D. ^{[1
,2
,7
]}

Xu, Jingsong ^{[1
,2
]}

机构：

[1] Univ Illinois, Coll Med, Dept Dermatol, Chicago, IL 60680 USA

[2] Univ Illinois, Coll Med, Dept Pharmacol, Chicago, IL USA

[3] Chinese Acad Sci, Inst Zool, Grad Sch, State Key Lab Biomembrane & Membrane Biotechnol, Beijing, Peoples R China

[4] Univ Illinois, Coll Med, Ctr Lung & Vasc Biol, Chicago, IL USA

[5] Univ Illinois, Coll Med, Dept Anesthesiol, Chicago, IL 60680 USA

[6] Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, Beijing 100080, Peoples R China

[7] Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200030, Peoples R China

来源：

NATURE IMMUNOLOGY | 2012年 / 13卷 / 05期

基金：

美国国家卫生研究院;

关键词：

FORMYL PEPTIDE RECEPTOR; SIGNALING PATHWAYS; CELL-MIGRATION; CHEMOTAXIS; POLARITY; ALPHA; BETA; PHOSPHORYLATION; DESENSITIZATION; SPECIFICITY;

D O I：

10.1038/ni.2258

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

To kill invading bacteria, neutrophils must interpret spatial cues, migrate and reach target sites. Although the initiation of chemotactic migration has been extensively studied, little is known about its termination. Here we found that two mitogen-activated protein kinases (MAPKs) had opposing roles in neutrophil trafficking. The extracellular signal-regulated kinase Erk potentiated activity of the G protein-coupled receptor kinase GRK2 and inhibited neutrophil migration, whereas the MAPK p38 acted as a noncanonical GRK that phosphorylated the formyl peptide receptor FPR1 and facilitated neutrophil migration by blocking GRK2 function. Therefore, the dynamic balance between Erk and p38 controlled neutrophil 'stop' and 'go' activity, which ensured that neutrophils reached their final destination as the first line of host defense.

引用

页码：457 / 464

页数：8

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