HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 48, 49825-49834, November 26, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/48/49825    most recent M406892200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hii, C. S. Articles by Ferrante, A. Search for Related Content PubMed PubMed Citation Articles by Hii, C. S. Articles by Ferrante, A. Social Bookmarking                      What's this?

Characterization of the MEK5-ERK5 Module in Human Neutrophils and Its Relationship to ERK1/ERK2 in the Chemotactic Response^*

Charles S. Hii¶, Donald S. Anson||, Maurizio Costabile**, Violet Mukaro**, Kylie Dunning||, and Antonio Ferrante**

From the Departments of Immunopathology and ^||Genetic Medicine, Women's and Children's Hospital, 72 King William Road, Adelaide SA5006, Australia, the ^**School of Pharmacy and Medical Sciences, University of South Australia, Frome Road, SA5000, Australia, and the Department of Pediatrics, University of Adelaide, North Terrace, SA5000, Australia

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.

Received for publication, June 21, 2004 , and in revised form, September 13, 2004.

^* This work was supported by a grant from the National Health and Medical Research Council of Australia and the Channel 7 Children's Research Foundation of South Australia. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed: Dept. of Immunopathology, Women's and Children's Hospital, 72 King William Rd., SA 5006, Australia. Tel.: 61-8-8161-6078; Fax: 61-8-8161-6046; E-mail: charles.hii{at}adelaide.edu.au.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. Tan, P. P. Dwivedi, P. Anderson, B. K. Nutchey, P. O'Loughlin, H. A. Morris, B. K. May, A. Ferrante, and C. S. Hii Antineoplastic agents target the 25-hydroxyvitamin D3 24-hydroxylase messenger RNA for degradation: implications in anticancer activity Mol. Cancer Ther., December 1, 2007; 6(12): 3131 - 3138. [Abstract] [Full Text] [PDF]

				A. M. Fusello, L. Mandik-Nayak, F. Shih, R. E. Lewis, P. M. Allen, and A. S. Shaw The MAPK Scaffold Kinase Suppressor of Ras Is Involved in ERK Activation by Stress and Proinflammatory Cytokines and Induction of Arthritis J. Immunol., November 1, 2006; 177(9): 6152 - 6158. [Abstract] [Full Text] [PDF]

				R. E. Schweppe, T. H. Cheung, and N. G. Ahn Global Gene Expression Analysis of ERK5 and ERK1/2 Signaling Reveals a Role for HIF-1 in ERK5-mediated Responses J. Biol. Chem., July 28, 2006; 281(30): 20993 - 21003. [Abstract] [Full Text] [PDF]

				Z. T. Kneass and R. B. Marchase Protein O-GlcNAc Modulates Motility-associated Signaling Intermediates in Neutrophils J. Biol. Chem., April 15, 2005; 280(15): 14579 - 14585. [Abstract] [Full Text] [PDF]