Mighty Deadly MyD88

Science's STKE  11 Jul 2000:
Vol. 2000, Issue 40, pp. tw3
DOI: 10.1126/stke.2000.40.tw3

Toll receptors are activated by bacterially produced pathogen-associated molecular pattern (PAMPs). Bacterial lipoproteins (BLPs) are PAMPs that activate the Toll-like receptor 2 (TLR2) through recruitment of the adaptor molecule MyD88. Transfection of a variety of dominant negative mutants allowed Aliprantis et al. to show that MyD88 is a common mediator for both the cell survival signal mediated by NF-κB activation and the apoptotic signal mediated through Fas-associated death domain protein (FADD). FADD activation is dependent on the death domain (DD) of MyD88, and the two proteins could be coimmunoprecipitated from transfected cells, confirming a physical interaction between them. Apoptosis was inhibited by mutant forms of caspase 8, FADD, or MyD88, confirming an apoptosis pathway from TLR2 to MyD88 to FADD to caspase 8.

Aliprantis, A.O., Yang, R.-B., Weiss, D.S., Godowski, P., and Zychlinsky, A. (2000) The apoptotic signaling pathway activated by Toll-like receptor-2. EMBO J. 19: 3325-3336. [Abstract] [Full Text]