Independent binding of interleukin-1 alpha and interleukin-1 beta to type I and type II interleukin-1 receptors.
Interleukin (IL)-1 refers to a group of three polypeptide hormones with a wide range of cellular targets. Two types of IL-1 receptor have been identified and characterized by cDNA cloning. Both human type I and type II IL-1 receptors contain extracellular domains of approximately 310 residues and a single membrane-spanning region. The type I receptor contains a cytoplasmic domain of 213 residues. The cytoplasmic region of the type II receptor is 29 residues in length. It has been found recently that a number of cells express both forms of receptor. By analogy with other cytokine receptor systems, the two IL-1 receptors might be expected to form a heterodimeric complex, the type II receptor being an alpha-chain-like structure, functioning only to bind ligand, and associating with the type I receptor (a beta-chain-like structure) which would transduce signals. In this report we show that this is not the case, but rather that IL-1, when complexed to type II receptor, cannot bind type I receptors, and vice versa. These data show that the complex patterns often observed for IL-1 binding to cells cannot be accounted for by the same type of mechanism that underlies the behavior of, for example, the IL-2 system.
Slack
J
J
Department of Biochemistry, Immunex Research and Development Corporation, Seattle, Washington 98101.
McMahan
C J
CJ
Waugh
S
S
Schooley
K
K
Spriggs
M K
MK
Sims
J E
JE
Dower
S K
SK
D000911:Antibodies, Monoclonal / Q000276:immunology; D001667:Binding, Competitive; D003432:Cross-Linking Reagents; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism*; D008024:Ligands; D046911:Macromolecular Substances; D017472:Receptors, Interleukin-1 / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012995:Solubility; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D007375:Interleukin-1; D008024:Ligands; D046911:Macromolecular Substances; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins