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Bidirectional regulation of neutrophil migration by mitogen-activated protein kinases

2012; Nature Portfolio; Volume: 13; Issue: 5 Linguagem: Inglês

10.1038/ni.2258

1529-2916

Xiaowen Liu, Bo Ma, Asrar B. Malik, Haiyang Tang, Tao Yang, Bo Sun, Gang Wang, Richard D. Minshall, Yan Li, Yong Zhao, Richard D. Ye, Jingsong Xu,

S100 Proteins and Annexins

Neutrophils are early responders and must navigate using spatial cues to arrive at infection sites. Xu and colleagues show that the opposing activities of MAP kinases Erk and p38 govern neutrophil migration. 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.