Bidirectional regulation of neutrophil migration by mitogen-activated protein kinases |
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Authors: | Liu Xiaowen Ma Bo Malik Asrar B Tang Haiyang Yang Tao Sun Bo Wang Gang Minshall Richard D Li Yan Zhao Yong Ye Richard D Xu Jingsong |
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Affiliation: | Department of Dermatology, University of Illinois College of Medicine, Chicago, Illinois, USA. |
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Abstract: | 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. |
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