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Threonine 66 in the death domain of IRAK‐1 is critical for interaction with signaling molecules but is not a target site for autophosphorylation
Author(s) -
Neumann Detlef,
Kollewe Christian,
Pich Andreas,
Cao Ping,
Resch Klaus,
Martin Michael U.
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0507290
Subject(s) - autophosphorylation , biology , threonine , signal transduction , microbiology and biotechnology , domain (mathematical analysis) , computational biology , phosphorylation , serine , protein kinase a , mathematical analysis , mathematics
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.