We investigated the coupling of the fMLP (N-formyl-l-methionyl-l-leucyl-l-phenylalanine; ‘chemotactic peptide’) receptor with phosphorylation of the actin-binding protein l-plastin in neutrophils. Using two-dimensional IEF (isoelectric focusing)/PAGE and MALDI–TOF (matrix-assisted laser desorption ionization–time-of-flight)-MS, l-plastin was identified as a major phosphoprotein in fMLP-stimulated neutrophils whose phosphorylation was dependent on phosphoinositide 3-kinase, PLD (phospholipase D) and PKC (protein kinase C) activity. Two fMLP receptor subtypes were identified in neutrophils, characterized by a distinct sensitivity to fMLP and antagonistic peptides. Both receptor subtypes induced the phosphorylation of l-plastin. l-plastin phosphorylation induced by low-affinity fMLP receptors involves an action of phosphoinositide 3-kinase, PLD and PKC isotypes. In contrast, none of these intermediates are utilized by high-affinity fMLP receptors in the phosphorylation of l-plastin. However, the PKC inhibitor Ro-31-8220 inhibits l-plastin phosphorylation induced by the high-affinity fMLP receptor. Thus, an as yet unknown Ro-31-8220-sensitive kinase regulates l-plastin phosphorylation in response to the high-affinity fMLP receptor. The results suggest a model in which receptor subtypes induce a similar endpoint event through different signal-transduction intermediates. This may be relevant in the context of cell migration in which one receptor subpopulation may become desensitized in a concentration gradient of chemoattractant.
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January 2004
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Research Article|
January 15 2004
N-Formyl peptide receptor subtypes in human neutrophils activate l-plastin phosphorylation through different signal transduction intermediates
Marie-Hélène PACLET;
Marie-Hélène PACLET
1
*Department of Medicine, Centre for Molecular Medicine, The Rayne Institute, University College London, 5 University Street, London WC1E 6JJ, U.K.
1To whom correspondence should be addressed. Present address: GREPI EA 2938, Laboratoire d'Enzymologie, C.H.U. Grenoble, B.P. 217, 38043 Grenoble Cedex 9, France (e-mail MHPaclet@chu-grenoble.fr).
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Clare DAVIS;
Clare DAVIS
†Novartis Institute for Medical Sciences, 5 Gower Place, London WC1E 6BS, U.K.
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Peter KOTSONIS;
Peter KOTSONIS
†Novartis Institute for Medical Sciences, 5 Gower Place, London WC1E 6BS, U.K.
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Jasminka GODOVAC-ZIMMERMANN;
Jasminka GODOVAC-ZIMMERMANN
*Department of Medicine, Centre for Molecular Medicine, The Rayne Institute, University College London, 5 University Street, London WC1E 6JJ, U.K.
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Anthony W. SEGAL;
Anthony W. SEGAL
*Department of Medicine, Centre for Molecular Medicine, The Rayne Institute, University College London, 5 University Street, London WC1E 6JJ, U.K.
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Lodewijk V. DEKKER
Lodewijk V. DEKKER
2
*Department of Medicine, Centre for Molecular Medicine, The Rayne Institute, University College London, 5 University Street, London WC1E 6JJ, U.K.
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Publisher: Portland Press Ltd
Received:
July 24 2003
Revision Received:
October 02 2003
Accepted:
October 13 2003
Accepted Manuscript online:
October 13 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2004
2004
Biochem J (2004) 377 (2): 469–477.
Article history
Received:
July 24 2003
Revision Received:
October 02 2003
Accepted:
October 13 2003
Accepted Manuscript online:
October 13 2003
Citation
Marie-Hélène PACLET, Clare DAVIS, Peter KOTSONIS, Jasminka GODOVAC-ZIMMERMANN, Anthony W. SEGAL, Lodewijk V. DEKKER; N-Formyl peptide receptor subtypes in human neutrophils activate l-plastin phosphorylation through different signal transduction intermediates. Biochem J 15 January 2004; 377 (2): 469–477. doi: https://doi.org/10.1042/bj20031114
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