Abstract
Cross-communication between GPCRs and TKRs represents a mechanism to amplify the information exchange throughout the cell. We show that WKYMVm, an FPR2 agonist, induces the phosphorylation of Y1313/Y1349/Y1356 residues of c-Met and triggers some of the molecular responses elicited by c-Met/HGF binding, such as STAT3, PLC-γ1/PKCα and PI3K/Akt pathways. The critical role of NADPH oxidase-dependent superoxide generation in this cross-talk mechanism is supported by the finding that blockade of NADPH oxidase function prevents c-Met trans-phosphorylation and the downstream signalling cascade. These results highlight the function of FPR2 to activate a interconnected signalling network and suggest novel possibilities for therapeutic interventions.
Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
MeSH terms
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Catalytic Domain / genetics
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Cell Line
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Epithelial Cells / cytology
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Epithelial Cells / drug effects
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Epithelial Cells / metabolism
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Humans
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Male
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Oligopeptides / pharmacology*
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Phosphorylation / drug effects
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Prostate / cytology
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Prostate / drug effects
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Prostate / metabolism*
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Proto-Oncogene Proteins c-met / antagonists & inhibitors
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Proto-Oncogene Proteins c-met / chemistry
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Proto-Oncogene Proteins c-met / genetics
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Proto-Oncogene Proteins c-met / metabolism*
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RNA, Small Interfering / pharmacology
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Receptor Cross-Talk / drug effects*
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Receptors, Formyl Peptide / agonists
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Receptors, Formyl Peptide / antagonists & inhibitors
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Receptors, Formyl Peptide / genetics
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Receptors, Formyl Peptide / metabolism*
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Receptors, Lipoxin / agonists
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Receptors, Lipoxin / antagonists & inhibitors
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Receptors, Lipoxin / genetics
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Receptors, Lipoxin / metabolism*
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Tyrosine / genetics
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Tyrosine / metabolism
Substances
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FPR2 protein, human
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Oligopeptides
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RNA, Small Interfering
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Receptors, Formyl Peptide
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Receptors, Lipoxin
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Trp-Lys-Tyr-Met-Val-Met
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Tyrosine
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Proto-Oncogene Proteins c-met