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Distinctly Similar Infection Signals

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Science  31 May 2002:
Vol. 296, Issue 5573, pp. 1573
DOI: 10.1126/science.296.5573.1573c

The Toll-like receptors 2 and 4 (TLR2 and TLR4) function in detection of bacterial infection, responding to lipoplysaccharide from Gram-negative bacteria or peptidoglycan from Gram-positive bacteria, respectively. Although the two receptors generate similar signaling outputs, evidence is accumulating that responses to the two are notably distinct. Carl et al. found that activation of either TLR2 or TLR4 enhanced expression of the secretory interleukin-1 receptor antagonist sIL-1Ra. In both cases, the transcription factor PU.1 was required for a full response, and pharmacological inhibition of the p38 stress-activated protein kinase showed that the kinase was required for full transcriptional activation. Nevertheless, the promoter regions required for the responses to TLR2 or TLR4 were different, and the p38-dependent response mapped to distinct regions of the promoter. The authors conclude that TLR2 and TL4 must activate different DNA binding proteins and that, even when using similar pathways (through p38 and PU.1), signals from the two receptors result in distinct gene regulatory responses. — LBR

J. Biol. Chem.277, 17448 (2002).

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