J Leukoc Biol. 2008 Sep;84(3):807-13. Epub 2008 Jun 4.

Threonine 66 in the death domain of IRAK-1 is critical for interaction with signaling molecules but is not a target site for autophosphorylation.External

Neumann, D., Kollewe, C., Pich, A., Cao, P., Resch, K., Martin, M. U.,
--- - Deptartment of Pharmacology, Hannover Medical School, Hannover, Germany. neumann.detlef@mh-hannover.de
Ligand binding in the TLR/IL-1R family results in the transient formation of an intracellular signaling complex, which contains, amongst others, the serine/threonine-specific kinase IL-1R-associated kinase 1 (IRAK-1). Concomitantly, the kinase function of IRAK-1 becomes activated, resulting in massive autophosphorylation and finally in the dissociation of the initially constituted signaling complex. The death domain (DD) of IRAK-1 mediates the interaction with other molecules of the signaling complex, e.g., the adaptor MyD88, the silencer Tollip, and the activator kinase IRAK-4. The conserved threonine at position 66 (T66), located within the DD, is a putative autophosphorylation target site. Here, we provide evidence that T66 critically impacts the secondary structure of the IRAK-1 DD. Thereby, it ensures the transient manner of interactions between IRAK-1 and the other signaling molecules. This essential role, however, is not regulated by phosphorylation of T66 itself.
PMID: 18524972External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DD IRAK1 Link IRAK4 Co-immunoprecipitation HEK293 Human 2-712 Not specified Not specified 18524972
DD IRAK1 Link Myd88 Co-immunoprecipitation HEK293 Human 2-712 Not specified Not specified 18524972
(Link: click this icon to show interactions only between the two corresponding DDs)