Multiple IRAK1 autophosphorylation steps

Stable Identifier
Reaction [transition]
Homo sapiens
Related Species
Chlamydia trachomatis, Neisseria meningitidis serogroup B
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Phosphorylation of IRAK-1 is due to three sequential phosphorylation steps, which leads 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 activated receptor complex. 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), It has been suggested that IRAK1 primarily acts as an adaptor for TRAF6 (Conze et al. 2008).

Literature References
PubMed ID Title Journal Year
14625308 Sequential autophosphorylation steps in the interleukin-1 Receptor-associated Kinase-1 Regulate its Availability as an Adapter in Interleukin-1 Signaling

Wesche, H, Li, S, Martin, MU, Knop, J, Neumann, D, Cao, P, Mackensen, AC, Kollewe, C

J Biol Chem 2004
Catalyst Activity

protein serine/threonine kinase activity of pp-IRAK1:p-IRAK4:oligo-MyD88:TIRAP:activated TLR [plasma membrane]

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