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Molecular Pharmacology

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Research ArticleArticle

Differential Activation of Formyl Peptide Receptor Signaling by Peptide Ligands

Yoe-Sik Bae, Ji Young Song, Youndong Kim, Rong He, Richard D. Ye, Jong-Young Kwak, Pann-Ghill Suh and Sung Ho Ryu
Molecular Pharmacology October 2003, 64 (4) 841-847; DOI: https://doi.org/10.1124/mol.64.4.841
Yoe-Sik Bae
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Ji Young Song
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Youndong Kim
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Rong He
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Richard D. Ye
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Jong-Young Kwak
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Pann-Ghill Suh
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Sung Ho Ryu
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Abstract

Formyl peptide receptor (FPR) and formyl peptide receptor like 1 (FPRL1) play important roles in inflammation and immunity. Stimulation of FPR and FPRL1 initiates a cascade of signaling events, leading to activation of various phagocyte responses, including chemotaxis, superoxide generation, and exocytosis. Trp-Lys-Tyr-Met-Val-d-Met-NH2 (WKYMVm) is a synthetic peptide that binds to and activates FPR and FPRL1. To develop agonists that selectively activate phagocyte functions and therefore protect host from unwanted tissue damage, we generated various WKYMVm analogs and examined their effects on cellular responses in FPR- or FPRL1-expressing RBL-2H3 cells. Analogs with substitution at the third position such as WKGMVm, WKRMVm, as well as analogs with substitution at the sixth d-Met, selectively altered calcium mobilization in cells expressing FPRL1 but not in cells expressing FPR. Whereas binding of WKYMVm to FPR activates a broad spectrum of cellular signaling events, including phospholipase C-mediated intracellular calcium concentration ([Ca2+]i) mobilization and activation of extracellular signal-regulated kinase (ERK) and Akt, WKGMVm and WKRMVm could only activate ERK and Akt but did not induce [Ca2+]i mobilization. With respect to phagocyte functions, WKYMVm could induce both chemotaxis and exocytosis, but the two analogs WKGMVm and WKRMVm could only induce chemotaxis but not exocytosis. This study demonstrates that a major phagocyte chemoattractant receptor FPR may be activated differentially by distinct peptide ligands. Our results suggest that WKGMVm and WKRMVm may be useful model for further development of pharmacological agents that selectively activate FPR-mediated functions.

  • Received May 5, 2003.
  • Accepted June 24, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 64 (4)
Molecular Pharmacology
Vol. 64, Issue 4
1 Oct 2003
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Research ArticleArticle

Differential Activation of Formyl Peptide Receptor Signaling by Peptide Ligands

Yoe-Sik Bae, Ji Young Song, Youndong Kim, Rong He, Richard D. Ye, Jong-Young Kwak, Pann-Ghill Suh and Sung Ho Ryu
Molecular Pharmacology October 1, 2003, 64 (4) 841-847; DOI: https://doi.org/10.1124/mol.64.4.841

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Research ArticleArticle

Differential Activation of Formyl Peptide Receptor Signaling by Peptide Ligands

Yoe-Sik Bae, Ji Young Song, Youndong Kim, Rong He, Richard D. Ye, Jong-Young Kwak, Pann-Ghill Suh and Sung Ho Ryu
Molecular Pharmacology October 1, 2003, 64 (4) 841-847; DOI: https://doi.org/10.1124/mol.64.4.841
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