TIRAP: an adapter molecule in the Toll signaling pathway

Mammalian Toll-like receptors (TLRs) recognize conserved products of microb ial metabolism and activate NF-kappaB and other signaling pathways through the adapter protein MyD88. Although some cellular responses are completely abolished in MyD88-deficient mice, TLR4, but not TLR9, can activate NF-KB a nd mitogen-activated protein kinases and induce dendritic cell maturation i n the absence of MyD88. These differences suggest that another adapter must exist that can mediate MyD88-independent signaling in response to TLR4 lig ation. We have identified and characterized a Toll-interleukin I receptor ( TIR) domain-containing adapter protein (TIRAP) and have shown that it contr ols activation of MyD88-independent signaling pathways downstream of TLR4. We have also shown that the double-stranded RNA-binding protein kinase PKR is a component of both the TIRAP- and MyD88-dependent signaling pathways.