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Formyl peptide receptor‐1 promotes intestinal epithelial cell migration by regulation of Vav2‐Rac1 signaling and ROS generation
Author(s) -
Leoni Giovanna,
Swanson P.,
Parks C.A.,
Neish A.,
Nusrat A.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.121.2
Subject(s) - microbiology and biotechnology , rac1 , cell migration , formyl peptide receptor , signal transduction , cdc42 , intestinal epithelium , motility , focal adhesion , biology , guanine nucleotide exchange factor , receptor , kinase , epithelium , cell , chemistry , biochemistry , genetics , chemotaxis
Intestinal epithelial cells have a remarkable capacity to migrate and efficiently reseal mucosal wounds that are characteristic of intestinal inflammatory diseases. In a recent study we reported that N‐formyl peptide receptor‐1 (FPR‐1) is expressed in the intestinal epithelium and functions to regulate cell motility and wound closure. However, the mechanisms of FPR‐1 induced epithelial cell migration are incompletely understood. Model intestinal epithelial cell lines were used to explore the signaling pathways by which FPR‐1 activation promotes cell migration. Exposure of epithelial cells to the FPR‐1 agonists, N‐formyl methionyl peptide (fMLF) and Annexin 1 N‐terminal peptide Ac2‐26, induced rapid activation of PI3K. This correlated with guanine nucleotide exchange factor, Vav2 association with active Rac1 GTPase and its down‐stream effector protein, Pak1. These events culminated in reactive oxygen species (ROS) generation and phosphorylation/activation of focal adhesion kinase (FAK) that in turn regulates cell migration. Taken together, these results support an important role for FPR‐1 stimulated signaling pathways in promoting intestinal epithelial cell migration and wound closure.