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

Protein Pept Lett. 2011 May;18(5):518-29. doi: 10.2174/092986611794927910.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Membrane / metabolism
  • Cytoskeletal Proteins / metabolism*
  • Epithelial Cells / metabolism*
  • Epithelial Cells / virology
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Protein Interaction Domains and Motifs
  • Protein-Tyrosine Kinases / metabolism*
  • Rhinovirus / pathogenicity*
  • Signal Transduction*
  • Syk Kinase
  • Transfection
  • src Homology Domains


  • Cytoskeletal Proteins
  • Intracellular Signaling Peptides and Proteins
  • ezrin
  • Intercellular Adhesion Molecule-1
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase