| First Author | Ley SC | Year | 2014 |
| Journal | Biochem J | Volume | 463 |
| Issue | 1 | Pages | e1-2 |
| PubMed ID | 25195736 | Mgi Jnum | J:215547 |
| Mgi Id | MGI:5605611 | Doi | 10.1042/BJ20140989 |
| Citation | Ley SC, et al. (2014) Priming IKKbeta kinase for action. Biochem J 463(1):e1-2 |
| abstractText | IKKbeta (IkappaB kinase beta) is a core component of signalling pathways that control the activation of NF-kappaB (nuclear factor kappaB) transcription factors, which regulate many physiological processes, including cell survival, immunity and DNA-damage responses. Like many kinases, activation of IKKbeta requires phosphorylation of the activation loop of its kinase domain. Different upstream protein kinases, and IKKbeta itself, have been reported to directly phosphorylate and activate IKKbeta in vitro, but the exact molecular mechanism of IKKbeta activation in cells has remained unclear. In a recent article in the Biochemical Journal, Zhang and co-workers showed that IKKbeta is activated by two sequential phosphorylations of its activation loop in response to TNF (tumour necrosis factor), IL-1 (interleukin-1) and TLR (Toll-like receptor) ligands. Using a combination of biochemical and genetic approaches, they demonstrate that IKKbeta is first phosphorylated by the upstream kinase TAK1 [TGFbeta (transforming growth factor beta)-activated kinase-1] at Ser177, which then serves as a priming signal for subsequent IKKbeta autophosphorylation at Ser181. This study resolves two apparently conflicting earlier models of IKKbeta activation into a single unified model, and suggests that the IKKbeta activation loop may integrate distinct 'upsteam' signals to activate NF-kappaB. |
