MyD88, an adapter protein involved in interleukin-1 signaling.

MyD88 has a modular organization, an N-terminal death domain (DD) related to the cytoplasmic signaling domains found in many members of the tumor necrosis factor receptor (TNF-R) superfamily, and a C-terminal Toll domain similar to that found in the expanding family of Toll/interleukin-1-like receptors (IL-1R). This dual domain structure, together ...
with the following observations, supports a role for MyD88 as an adapter in IL-1 signal transduction; MyD88 forms homodimers in vivo through DD-DD and Toll-Toll interactions. Overexpression of MyD88 induces activation of the c-Jun N-terminal kinase (JNK) and the transcription factor NF-kappaB through its DD. A point mutation in MyD88, MyD88-lpr (F56N), which prevents dimerization of the DD, also blocks induction of these activities. MyD88-induced NF-kappaB activation is inhibited by the dominant negative versions of TRAF6 and IRAK, which also inhibit IL-1-induced NF-kappaB activation. Overexpression of MyD88-lpr or MyD88-Toll (expressing only the Toll domain) acted to inhibit IL-1-induced NF-kappaB and JNK activation in a 293 cell line overexpressing the IL-1RI. MyD88 coimmunoprecipitates with the IL-1R signaling complex in an IL-1-dependent manner.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Antigens, Differentiation, Calcium-Calmodulin-Dependent Protein Kinases, Cell Line, Dimerization, Enzyme Activation, Humans, Interleukin-1, JNK Mitogen-Activated Protein Kinases, Mice, Mitogen-Activated Protein Kinases, Myeloid Differentiation Factor 88, NF-kappa B, Proteins, Receptors, Immunologic, Recombinant Proteins, Signal Transduction
J. Biol. Chem.
Date: May. 15, 1998
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