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Göteborgs universitets publikationer

Structural Characterization and Inhibitory Profile of Formyl Peptide Receptor 2 Selective Peptides Descending from a PIP2-Binding Domain of Gelsolin.

Författare och institution:
Huamei Forsman (Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning); Emil Andréasson (Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning); Jennie Karlsson (Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning); Francois Boulay (-); Marie-Josèphe Rabiet (-); Claes Dahlgren (Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning)
Publicerad i:
Journal of immunology (Baltimore, Md. : 1950), 189 ( 2 ) s. 629-637
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
The neutrophil formyl peptide receptors, FPR1 and FPR2, play critical roles for inflammatory reactions, and receptor-specific antagonists/inhibitors can possibly be used to facilitate the resolution of pathological inflammatory reactions. A 10-aa-long rhodamine-linked and membrane-permeable peptide inhibitor (PBP10) has such a potential. This FPR2 selective inhibitor adopts a phosphatidylinositol 4,5-bisphosphate-binding sequence in the cytoskeletal protein gelsolin. A core peptide, RhB-QRLFQV, is identified that displays inhibitory effects as potent as the full-length molecule. The phosphatidylinositol 4,5-bisphosphate-binding capacity of PBP10 was not in its own sufficient for inhibition. A receptor in which the presumed cytoplasmic signaling C-terminal tail of FPR2 was replaced with that of FPR1 retained the PBP10 sensitivity, suggesting that the tail of FPR2 was not on its own critical for inhibition. This gains support from the fact that the effect of cell-penetrating lipopeptide (a pepducin), suggested to act primarily through the third intracellular loop of FPR2, was significantly inhibited by PBP10. The third intracellular loops of FPR1 and FPR2 differ in only two amino acids, but an FPR2 mutant in which these two amino acids were replaced by those present in FPR1 retained the PBP10 sensitivity. In summary, we conclude that the inhibitory activity on neutrophil function of PBP10 is preserved in the core sequence RhB-QRLFQV and that neither the third intracellular loop of FPR2 nor the cytoplasmic tail of the receptor alone is responsible for the specific inhibition.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Medicinska grundvetenskaper
Postens nummer:
Posten skapad:
2012-07-09 14:49
Posten ändrad:
2012-07-09 16:20

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