IRAK4-activated IRAK1 autophosphorylates A series of sequential phosphorylation events lead to full or hyper-phopshorylation of IRAK1. Under in vitro conditions these are all autophosphorylation events. First, Thr-209 is phosphorylated resulting in a conformational change of the kinase domain. Next, Thr-387 in the activation loop is phosphorylated, leading to full enzymatic activity. Several additional residues are phosphorylated in the proline-, serine-, and threonine-rich (ProST) region between the N-terminal death domain and kinase domain. Hyperphosphorylation of this region leads to dissociation of IRAK1 from the upstream adapters MyD88 and Tollip. The significance of these phosphorylation events is not clear; the kinase activity of IRAK1 is dispensable for IL1-induced NFkB and MAP kinase activation (Knop & Martin, 1999), unlike that of IRAK4 (Suzuki et al. 2002; Kozicak-Holbro et al. 2007), so IRAK1 is believed to act primarily as an adaptor for TRAF6 (Conze et al. 2008). Authored: Ray, KP, 2010-05-17 EC Number: 2.7.11 Edited: Jupe, S, 2010-05-17 Pubmed10217414 Pubmed11923871 Pubmed14625308 Pubmed17337443 Pubmed18347055 Reactome Database ID Release 43446701 Reactome, http://www.reactome.org ReactomeREACT_22162 Reviewed: Pinteaux, E, 2010-05-17 has a Stoichiometric coefficient of 4 IL1 receptor complex- activated IRAK4:TOLLIP:p-IRAK1 IL1 receptor complex- activated IRAK4:TOLLIP:hp-IRAK1