P2Y2 RECEPTOR PEPDUCINS HIJACK AND ACTIVATE THE FORMYL PEPTIDE RECEPTOR 2 IN HUMAN NEUTROPHILS

Examensarbete för masterexamen

Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12380/218571
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Type: Examensarbete för masterexamen
Master Thesis
Title: P2Y2 RECEPTOR PEPDUCINS HIJACK AND ACTIVATE THE FORMYL PEPTIDE RECEPTOR 2 IN HUMAN NEUTROPHILS
Authors: Holdfeldt, André
Abstract: Neutrophils are the most abundant phagocytic cell type and have a critical role in the innate immune system. They are attracted to the site of infection/inflammation through a number of surface expressing chemoattractant G-protein coupled receptors (GPCRs). Activation of neutrophil GPCRs mediates not only directional migration, but also triggers the release of reactive oxygen species and granule stored enzymes. The formyl peptide receptor 1 (FPR1), displaying high binding affinity for the “danger signal” formyl peptides derived from bacteria or damaged mitochondria, was the first chemoattractant GPCRs cloned and has therefore served as a model receptor for our understanding of neutrophil physiology. In addition to FPR1, neutrophils express also the closely related formyl peptide receptor 2 (FPR2) and the danger signaling ATP recognition receptor (P2Y2-R). All GPCRs share a similar seven transmembrane helical structure in which the extracellular domains are involved in ligand binding whereas the intracellular parts are engaged in G-protein coupling and signaling transduction. Recent research has proposed a group of cell penetrating molecules, so called pepducins that can modulate GPCR signaling from the inside. Pepducins are lipopeptides derived from one of the intracellular lopes of a GPCR, they are supposed to allosterically activate or inhibit the receptor from it is derived. In this study, we investigated the ATP receptor signaling by applying pepducins from the P2Y2 receptor. Our data show that these pepducins do not target their cognate receptor as the currently “pepducin model” proposed and instead activate FPR2. This “model” has also been challenged by the recent findings from pepducins from FPR1 and β2-adrenergic receptor
Keywords: Livsvetenskaper;Biokemi och molekylärbiologi;Life Science;Biochemistry and Molecular Biology
Issue Date: 2015
Publisher: Chalmers tekniska högskola / Institutionen för biologi och bioteknik
Chalmers University of Technology / Department of Biology and Biological Engineering
URI: https://hdl.handle.net/20.500.12380/218571
Collection:Examensarbeten för masterexamen // Master Theses



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