Research ArticleImmunology

Epidermal Growth Factor Receptor Is Essential for Toll-Like Receptor 3 Signaling

Sci. Signal.  17 Jul 2012:
Vol. 5, Issue 233, pp. ra50
DOI: 10.1126/scisignal.2002581

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A Growth Factor Receptor Takes Its Toll

Toll-like receptor 3 (TLR3) initiates innate immune responses to double-stranded RNA (dsRNA) released by viruses or apoptotic cells. Activation of TLR3 requires phosphorylation of two tyrosine residues in its cytoplasmic domain. Yamashita et al. identified the tyrosine kinases involved and dissected the temporal sequence of these phosphorylation events. In response to dsRNA, TLR3 was phosphorylated by the epidermal growth factor receptor ErbB1, a receptor tyrosine kinase that triggers cellular proliferation in response to ligand binding. This phosphorylation event was required to trigger phosphorylation of TLR3 at a different site by the tyrosine kinase Src. In cells lacking EGFR or treated with an inhibitor of EGFR, the TLR3-mediated antiviral response was impaired. These results indicate that TLR3-mediated antiviral responses require tyrosine kinases with established roles in regulating cell growth.