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• W2090414357 endingPage "487" @default.
• W2090414357 startingPage "482" @default.
• W2090414357 abstract "Peptides simultaneously produced during maturation and degradation of peptidergic hormones and functional proteins have recently become a great interest because they display unpredictably different biological roles than the parent proteins. Namely, we discovered two novel functional cryptic peptides, mitocryptide-1 (MCT-1) and mitocryptide-2 (MCT-2), hidden in mitochondrial cytochrome c oxidase and cytochrome b, that efficiently induced neutrophilic migration and activation at nanomolar concentrations. We named these functional “cryptic” peptides hidden in protein structures as “cryptides.” In this study, we investigated the receptor molecules and cellular signaling mechanisms for neutrophil-activating N-formylated cryptide MCT-2. In order to identify the receptor molecules, we established HEK-293 cells stably expressing either formyl-peptide receptor (FPR) or its homologue FPR-like 1 (FPRL1), because neutrophilic cells express these receptor molecules which recognize N-formylated peptides. We observed that MCT-2 directly bound to FPRL1 and promoted an increase in intracellular Ca2+ concentration ([Ca2+]i), and neither interacted with nor activated FPR, demonstrating that MCT-2 is a specific agonist for FPRL1. Moreover, MCT-2 induced not only [Ca2+]i increase and phosphorylation of extracellular signal-regulated protein kinases 1 and 2, but also β-hexosaminidase release in neutrophilic/granulocytic cells differentiated from HL-60 cells. Such signaling events were diminished by pretreatment with pertussis toxin, indicating that MCT-2-promoted neutrophilic function is a consequence of Gi- or Go-type G protein-dependent intracellular signaling events via FPRL1 activation. These findings suggest that MCT-2, a cryptide derived from mitochondrial cytochrome b, is a specific endogenous agonist for FPRL1 which is proposed to play key roles in inflammatory responses but whose physiological agonists are equivocal." @default.
• W2090414357 created "2016-06-24" @default.
• W2090414357 creator A5006557735 @default.
• W2090414357 creator A5036145665 @default.
• W2090414357 creator A5057587673 @default.
• W2090414357 creator A5063610442 @default.
• W2090414357 date "2011-01-01" @default.
• W2090414357 modified "2023-10-17" @default.
• W2090414357 title "Mitocryptide-2, a neutrophil-activating cryptide, is a specific endogenous agonist for formyl-peptide receptor-like 1" @default.
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• W2090414357 doi "https://doi.org/10.1016/j.bbrc.2010.12.007" @default.
• W2090414357 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21144840" @default.
• W2090414357 hasPublicationYear "2011" @default.
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