Open AccessRhinoviral Infections Activate p38MAP-Kinases Via Membrane Rafts and RhoA
Author(s) -
Claudia A. Dumitru,
Stephan Dreschers,
Erich Gulbins
Publication year - 2006
Publication title -
cellular physiology and biochemistry
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000092077
Subject(s) - rhoa , lipid raft , microbiology and biotechnology , p38 mitogen activated protein kinases , small gtpase , transfection , biology , kinase , signal transduction , cell culture , protein kinase a , genetics
Rhinoviral infections belong to the most frequent human infections characterized by common cold, chronic bronchitis, exacerbations of asthma, otitis media and sinusitis. Here, we define molecular mechanisms that mediate infections of human epithelial cells with human rhinovirus strain 14 (RV14). We demonstrate that RV14 activates p38-MAPKinase (p38-K) in a biphasic time course. Early stimulation of p38-K by RV14 was observed a few minutes after initiation of the infection, while the late increase of p38-K activity occurred 7-12 hrs upon infection. The stimulation of p38-K was mediated by the small G-protein RhoA,which was activated by RV14. Transfection of a genetic construct preventing RhoA activation blocked RV14-induced p38-K activation. Further, integrity of cholesterol and sphingolipid-enriched membrane domains was required for RV14-mediated p38-K activation, which was inhibited by destruction of membrane rafts. The data indicate that RV employs a signaling cascade from membrane rafts via the small G-protein RhoA to p38-K to infect human cells.