Serine/threonine kinase PKR: A sentinel kinase that discriminates a signaling pathway mediated by TLR4 from those mediated by TLR3 and TLR9

Cells of the innate immune system discriminate between "noninfectious self" and "infectious nonself" via pattern recognition receptors known as Toll-like receptors (TLRs). Though TLRs and the related interleukin 1 receptors share considerable homology in their cytoplasmic domains and adaptor molecules, signaling cascades may substantially differ from one another depending on the adaptor proteins recruited. Here we show that ectopic overexpression of catalytically inactive dominant-negative PKR expression system suppressed NF-κB activation mediated by TLR3, TLR9, TNF receptor 1 and 2 (TNF-R 1/2), but not by TLR4. Physiological relevance of the observations described here are discussed.