J Biol Chem. 1995 Jan 6;270(1):387-91.

Self-association of the "death domains" of the p55 tumor necrosis factor (TNF) receptor and Fas/APO1 prompts signaling for TNF and Fas/APO1 effects.External

Boldin, M. P., Mett, I. L., Varfolomeev, E. E., Chumakov, I., Shemer-Avni, Y., Camonis, J. H., Wallach, D.,
--- - Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot, Israel.
Signaling by the p55 tumor necrosis factor (TNF) receptor and by the structurally related receptor Fas/APO1 is initiated by receptor clustering. Data presented here and in other recent studies (Wallach, D., Boldin, M., Varfolomeev, E. E., Bigda, Y., Camonis, H.J. and Mett, I. (1994) Cytokine 6, 556; Song, H.Y., Dunbar, J.D., and Bonner, D.B. (1994) J. Biol. Chem. 269, 22492-22495) indicate that part of that region within the intracellular domains of the two receptors that is involved in signaling for cell death, as well as for some other effects (the "death domain", specifically self-associates. We demonstrate also the expected functional consequence of this association; a mere increase in p55 TNF receptor expression, or the expression just of its intracellular domain, is shown to trigger signaling for cytotoxicity as well as for interleukin 8 gene induction, while expression of the intracellular domain of Fas/APO1 potentiates the cytotoxicity of co-expressed p55 TNF receptor. These findings indicate that the p55 TNF and Fas/APO1 receptors play active roles in their own clustering and suggest the existence of cellular mechanisms that restrict the self-association of these receptors, thus preventing constitutive signaling.
PMID: 7529234External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vitro interaction
  DD1 DD2 Reference
Family DD1 DD2 Method Species Region Expression Species Region Expression
DD TNFR1 Link TNFR1 GST fusion protein pull-down Human 206-426 Not specified Human 206-426 Not specified 7529234
DD TNFR1 Link TNFR1 Yeast two-hybrid Human 206-426 Yeast Human 206-426 Yeast 7529234
DD TNFR1 Link TNFR1 Yeast two-hybrid Human 206-426 Yeast Human 328-426 Yeast 7529234
(Link: click this icon to show interactions only between the two corresponding DDs)