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Type: Journal article
Title: Characterization of the MEK5-ERK5 module in human neutrophils and its relationship to ERK1/ERK2 in the chemotactic response
Author: Hii, C.
Anson, D.
Costabile, M.
Mukaro, V.
Dunning, K.
Ferrante, A.
Citation: Journal of Biological Chemistry, 2004; 279(48):49825-49834
Publisher: Amer Soc Biochemistry Molecular Biology Inc
Issue Date: 2004
ISSN: 0021-9258
Statement of
Charles S. Hii, Donald S. Anson, Maurizio Costabile, Violet Mukaro, Kylie Dunning, and Antonio Ferrante
Abstract: The role of the extracellular signal-regulated kinase (ERK) 1 and ERK2 in the neutrophil chemotactic response remains to be identified since a previously used specific inhibitor of MEK1 and MEK2, PD98059, that was used to provide evidence for a role of ERK1 and ERK2 in regulating chemotaxis, has recently been reported to also inhibit MEK5. This issue is made more critical by our present finding that human neutrophils express mitogen-activated protein (MAP) kinase/ERK kinase (MEK)5 and ERK5 (Big MAP kinase), and that their activities were stimulated by the bacterial tripeptide, formyl methionyl-leucyl-phenylalanine (fMLP). Dose response studies demonstrated a bell-shaped profile of fMLP-stimulated MEK5 and ERK5 activation, but this was left-shifted when compared with the profile of fMLP-stimulated chemotaxis. Kinetics studies demonstrated increases in kinase activity within 2 min, peaking at 3-5 min, and MEK5 activation was more persistent than that of ERK5. There were some similarities as well as differences in the pattern of activation between fMLP-stimulated ERK1 and ERK2, and MEK5-ERK5 activation. The up-regulation of MEK5-ERK5 activities was dependent on phosphatidylinositol 3-kinase. Studies with the recently described specific MEK inhibitor, PD184352, at concentrations that inhibited ERK1 and ERK2 but not ERK5 activity demonstrate that the ERK1 and ERK2 modules were involved in regulating fMLP-stimulated chemotaxis and chemokinesis. Our data suggest that the MEK5-ERK5 module is likely to regulate neutrophil responses at very low chemoattractant concentrations whereas at higher concentrations, a shift to the ERK1/ERK2 and p38 modules is apparent.
Keywords: Neutrophils; Humans; Hydrogen Peroxide; MAP Kinase Kinase 5; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinase 7; Polymerase Chain Reaction; Chemotaxis
Rights: © 2004 by The American Society for Biochemistry and Molecular Biology, Inc.
RMID: 0020041001
DOI: 10.1074/jbc.M406892200
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Appears in Collections:Paediatrics publications

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