Cell Signaling

Toll-Like Receptor Tag Team

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Science  27 Jul 2012:
Vol. 337, Issue 6093, pp. 391
DOI: 10.1126/science.337.6093.391-b

How many receptors does it take to initiate an antiviral response? Yamashita et al. say it's two, plus an additional tyrosine kinase. First, you need Toll-like Receptor 3 (TLR3), which has a well-characterized role in the detection of double-stranded RNA (dsRNA) and initiation of protective cellular responses. Earlier findings showed that TLR3 differs from other TLRs in requiring phosphorylation of two tyrosine residues in its cytoplasmic tail for activation. Here, another receptor is implicated in the activation of antiviral responses by TLR3—the epidermal growth factor receptor (EGFR), which is itself a tyrosine kinase. The EGFR was found to associate with dsRNA-activated TLR3 in endosomal membranes along with another tyrosine kinase, Src. Both EGFR and Src appeared to phosphorylate a particular tyrosine residue in TLR3, and inhibition of the kinases inhibited TLR3-dependent antiviral responses. Thus, antiviral responses may involve interactions between signaling systems controlling cell growth and those mediating innate immune responses.

Sci. Signal. 5, ra50 (2012).

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