A critical role for interleukin-1 receptor accessory protein in interleukin-1 signaling.
Interleukin-1 (IL-1) is a central molecule in inflammation and immune responses whose pleiotropic activities are mediated by the type I IL-1 receptor (IL-1RI). The IL-1RI alone on the cell surface is silent after binding of the ligand. We show that the recently identified IL-1RI accessory protein (IL-1RAcP) converts the silent into a fully functional IL-1RI complex. Although transfection of IL-1RAcP into IL-1RAcP-deficient EL4D6/76 cells did not alter the binding kinetics or dissociation constants of the 125I-labeled IL-1alpha/IL-1RI complex, a very early event, internalization of the activated receptor complex, and a late event, IL-1-stimulated IL-2 production, were successfully restored. Therefore, recruitment of IL-1RAcP is a critical early step in the signaling cascade mediated by the IL-1RI activation complex.
Korherr
C
C
Department of Internal Medicine I, University of Regensburg, Germany.
Hofmeister
R
R
Wesche
H
H
Falk
W
W
D000818:Animals; D002478:Cells, Cultured; D004705:Endocytosis; D007375:Interleukin-1 / Q000502:physiology*; D053577:Interleukin-1 Receptor Accessory Protein; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D011506:Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection
C507767:Il1rap protein, mouse; D007375:Interleukin-1; D053577:Interleukin-1 Receptor Accessory Protein; D007376:Interleukin-2; D011506:Proteins; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1