Interleukin-1 receptor accessory protein interacts with the type II interleukin-1 receptor.
Stably transfected HEK-293 cells express on their surface the murine type II IL-1 receptor (mIL-1RII) as demonstrated by FACS analysis using the mAb 4E2, however binding of [125I]-hrIL-1beta to these cells is nearly absent. Saturable high affinity binding of [125I]-hrIL-1beta is observed when the murine IL-1 receptor accessory protein (mIL-1RAcP) is coexpressed with mIL-1RII. Binding of [125I]-hrIL-1beta to mIL-1RII-mIL-1RAcP complex can be inhibited either with antibodies to mIL-1RII (mAb 4E2), or by antibodies to mIL-1RAcP (mAb 4C5). The number of high affinity binding sites in cells stably transfected with the cDNA for mIL-1RII is dependent on the dose of cDNA for mIL-1RAcP used to transfect the cells. The high affinity complex between mIL-1RII and mIL-1RAcP is not preformed by interaction between the intracellular domains of these two transmembrane proteins, rather it appears to require the extracellular portions of mIL-1RII and mIL-1RAcP and the presence of a ligand. We suggest that in addition to its earlier described decoy receptor role, IL-1RII may modulate the responsiveness of cells to IL-1 by binding the IL-1RAcP in unproductive/non-signalling complexes and thus reducing the number of signalling IL-1RI-IL-1RAcP-agonist complexes when IL-1 is bound.
Malinowsky
D
D
Department of Neurochemistry and Neurotoxicology, The Arrhenius Laboratories for Natural Sciences, Stockholm University, Sweden.
Lundkvist
J
J
Layé
S
S
Bartfai
T
T
D000818:Animals; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D053577:Interleukin-1 Receptor Accessory Protein; D051379:Mice; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D053574:Receptors, Interleukin-1 Type II; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
C507765:IL1RAP protein, human; C507767:Il1rap protein, mouse; D007375:Interleukin-1; D053577:Interleukin-1 Receptor Accessory Protein; D011506:Proteins; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D011994:Recombinant Proteins