Although RLR-mediated signaling to NFkB and MAPK shares similarity with better-characterized TLR and TNF signaling pathways, many of the details need to be clarified. Thus, TGF-beta activated kinase 1(TAK1, also known as MAP3K7) - an essential mediator in TLR signaling downstream of TRAF6, was shown to associate with IPS-1 [Xu LG et al 2005]. However, there are conflicting reports on the role of TAK1 in RIG-1/IPS-1 mediated NFkB activation [Konno H et al 2009, Yoshida R et al 2008, Mikkelsen SS et al 2009].
Another MAP3K, MEKK1, has been reported to induce IKK and MAPK activation in RIG1 signaling pathway in response to dsRNA.[Yoshida R et al 2008].
TNF receptor associated factor (TRAF) protein family members are E3 ligases that have been implicated in various signal transduction pathways including RLR signaling and Toll-like receptors (TLRs) leading to activation of NFkB, MAPK and IRF family members [Oganesyan G et al 2006, Xia et al 2009, Sasai M et al 2010].