Characterization of Pellino2, a substrate of IRAK1 and IRAK4

Interleukin-1 (IL-1) receptor-associated kinases (IRAKs) are central components of Toll/IL-1 receptor (TIR) signaling pathways. In an attempt to discover novel signal transducers in TIR signaling, we identified human Pellino2 as an interaction partner of IRAK4. Pellino2 interacts with kinase-active as well as kinase-inactive IRAK1 and IRAK4. Furthermore, Pellino2 is one of the first substrates identified for IRAK1 and IRAK4. Functional studies using overexpression or RNAi knock-down of Pellino2 suggest a role of Pellino2 as a scaffolding protein similar to Pellino1. However, unlike Pellino1, Pellino2 does not seem to activate a specific transcription factor, but links TIR signaling to basic cellular processes.