Multiple IRAK1 autophosphorylation within the complex p-IRAK4:oligo MyD88:activated TLR

Stable Identifier
R-HSA-975853
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Escherichia coli
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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).

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

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

J Biol Chem 2004
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Catalyst Activity
Catalyst Activity
Title
protein serine/threonine kinase activity of pp-IRAK1:p-IRAK4:oligo-MyD88 :activated TLR5 or 10 complex [plasma membrane]
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