RRC ID 17487
Author Liu X, Ma B, Malik AB, Tang H, Yang T, Sun B, Wang G, Minshall RD, Li Y, Zhao Y, Ye RD, Xu J.
Title Bidirectional regulation of neutrophil migration by mitogen-activated protein kinases.
Journal Nat. Immunol.
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.
Volume 13(5)
Pages 457-64
Published 2012-3-25
DOI 10.1038/ni.2258
PII ni.2258
PMID 22447027
PMC PMC3330201
MeSH Animals Chemotaxis, Leukocyte* Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors Extracellular Signal-Regulated MAP Kinases / metabolism* Flavonoids / pharmacology G-Protein-Coupled Receptor Kinase 2 / metabolism* HEK293 Cells HL-60 Cells Humans Imidazoles / pharmacology Mice Mice, Knockout N-Formylmethionine Leucyl-Phenylalanine / metabolism Neutrophils / drug effects Neutrophils / enzymology Neutrophils / immunology* Pyridines / pharmacology Receptors, Formyl Peptide / metabolism* Signal Transduction / drug effects Signal Transduction / physiology p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors p38 Mitogen-Activated Protein Kinases / metabolism*
IF 21.809
Times Cited 78
Mice p38α-flox マウス