Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12654-8. Epub 2001 Oct 16.

Drosophila MyD88 is an adapter in the Toll signaling pathway.External

Horng, T., Medzhitov, R.,
--- - Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Toll-like receptors comprise a family of cell surface receptors that play a crucial role in the innate immune recognition of both Drosophila and mammals. Previous studies have shown that Drosophila Toll-1 mediates the induction of antifungal peptides during fungal infection of adult flies. Through genetic studies, Tube, Pelle, Cactus, and Dif have been identified as downstream components of the Toll-1 signaling pathway. Here we report characterization of a Drosophila homologue of human MyD88, dMyD88. We show that dMyD88 is an adapter in the Toll signaling pathway that associates with both the Toll receptor and the downstream kinase Pelle. Expression of dMyD88 in S2 cells strongly induced activity of a Drosomycin reporter gene, whereas a dominant-negative version of dMyD88 potently inhibited Toll-mediated signaling. We also show that dMyD88 associates with the death domain-containing adapter Drosophila Fas-associated death domain-containing protein (dFADD), which in turn interacts with the apical caspase Dredd. This pathway links a cell surface receptor to an apical caspase in invertebrate cells and therefore suggests that the Toll-mediated pathway of caspase activation may be the evolutionary ancestor of the death receptor-mediated pathway for apoptosis induction in mammals.
PMID: 11606776External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DD FADD Link Myd88 Co-immunoprecipitation Drosophila S2 Drosophila Not specified Drosophila 1-237 11606776
(Link: click this icon to show interactions only between the two corresponding DDs)