title: Bidirectional regulation of neutrophil migration by mitogen-activated protein kinases.
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.
authors.affiliation: Department of Dermatology, University of Illinois College of Medicine, Chicago, Illinois, USA.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liu
authors.forename: Bo
authors.initials: B
authors.lastname: Ma
authors.forename: Asrar B
authors.initials: AB
authors.lastname: Malik
authors.forename: Haiyang
authors.initials: H
authors.lastname: Tang
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Richard D
authors.initials: RD
authors.lastname: Minshall
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Richard D
authors.initials: RD
authors.lastname: Ye
authors.forename: Jingsong
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D002634:Chemotaxis, Leukocyte; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000378:metabolism*; D057809:HEK293 Cells; D018922:HL-60 Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D011725:Pyridines / Q000494:pharmacology; D044042:Receptors, Formyl Peptide / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C469986:FPR1 protein, human; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; D044042:Receptors, Formyl Peptide; D009240:N-Formylmethionine Leucyl-Phenylalanine; C496567:GRK2 protein, human; D054769:G-Protein-Coupled Receptor Kinase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one