Threonine 66 in the death domain of IRAK-1 is critical for interaction with signaling molecules but is not a target site for autophosphorylation |
| |
Authors: | Neumann Detlef Kollewe Christian Pich Andreas Cao Ping Resch Klaus Martin Michael U |
| |
Institution: | Dept. of Pharmacology OE 5320, Carl-Neuberg-Str.1, D-30625 Hannover, Germany. neumann.detlef@mh-hannover.de. |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|