Figure 1

IRAK1 kinase drives distinct prosurvival responses to microbial infection and ionizing radiation. (A) Diagram of the TLR signaling cascade which stimulates immune cell survival and inflammation in response to pathogen sensing. Ligated TLRs recruit MyD88 to trigger Myddosome (MyD88-IRAK4-IRAK1) formation, resulting in the activation of IRAK1 and release of the kinase from the complex. In turn, the activated form of IRAK1 binds TRAF6 to enable TRAF6-mediated activation of multiple pathways involved in anti-apoptotic and pro-inflammatory signaling. (B) Diagram of the newly identified IRAK1 signaling pathway triggered by IR, which involves IRAK4 but not MyD88 and antagonizes apoptosis through a different route involving inhibition of PIDDosome formation. Note that while IRAK1 catalytic activity is required in the radiation response (as symbolized by a green glare), it is dispensable for microbial responses relying on TRAF6 as signaling intermediate downstream of IRAK1.