Interleukin-1 (IL-1) receptor antagonist binds to the 80-kDa IL-1 receptor but does not initiate IL-1 signal transduction.
The interleukin-1 receptor antagonist (IL-1ra) is a protein capable of inhibiting receptor binding and biological activities of IL-1 without inducing an IL-1-like response. Equilibrium binding and kinetic experiments show that IL-1ra binds to the 80-kDa IL-1 receptor on the murine thymoma cell line EL4 with an affinity (KD = 150 pM) approximately equal to that of IL-1 alpha and IL-1 beta for this receptor. However, IL-1ra is unable to induce two early events associated with IL-1 activity. Surface-bound IL-1ra does not undergo receptor-mediated internalization, and IL-1ra does not activate the protein kinase activity responsible for down-modulation of the EGF receptor on the murine 3T3 fibroblast cell line. The failure to induce general, early responses characteristic of IL-1 indicates that IL-1ra is unlikely to act as an agonist on any cell expressing the 80-kDa receptor.
Dripps
D J
DJ
Synergen, Inc., Boulder, Colorado 80301.
Brandhuber
B J
BJ
Thompson
R C
RC
Eisenberg
S P
SP
D000818:Animals; D001665:Binding Sites; D015536:Down-Regulation; D004790:Enzyme Induction; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000187:drug effects; D007375:Interleukin-1 / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D011494:Protein Kinases / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000187:drug effects* / Q000378:metabolism; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D011494:Protein Kinases; D066246:ErbB Receptors