HRV signaling in airway epithelial cells is regulated by ITAM-mediated recruitment and activation of Syk

Human rhinovirus (hrv),cause of the common cold,is a leading cause of exacerbations of asthma and chronic obstruction pulmonary disease (copd). binding of hrv to icam (intercellular adhesion molecule)-1,its major receptor,induces a profound inflammatory response from airway epithelial cells. my laboratory has identified syk tyrosine kinase to be an early regulator of hrv-icam-1 signalling: syk mediates replication-independent p38 mitogen-activated protein (map) kinase and phosphatidyl-inositol 3 (pi3)-kinase activation,interleukin (il)-8 expression,as well as hrv internalization via clathrin-mediated endocytosis. syk activation is accompanied by formation of a protein complex consisting of icam-1,ezrin and syk at the plasma membrane. however,the molecular mechanisms that regulate this process are not understood. in this report,we investigated the role of the syk-sh2 domains and the ezrin-itam (immuno-tyrosine activation motif)-like motif in hrv-induced cell activation using the human beas-2b airway epithelial cells. our observations suggest that the ezrin-itam plays a role in syk recruitment and activation by binding to the syk tandem sh2 domains,as originally described in the canonical itam-mediating signal transduction pathway in hematopoietic cells. this report is the first to demonstrate itam-mediated signaling in non-hematopoietic cells,suggesting that this signaling paradigm may be more ubiquitous than previously recognized. copyright © 2011 bentham science publishers ltd.