Expression cloning of a human IL-12 receptor component. A new member of the cytokine receptor superfamily with strong homology to gp130.

By A. O. Chua, R. Chizzonite, B. Desai, T. Truitt, P. Nunes, L. Minetti, R. Warrier, D. Presky, J. Levine, M. Gately. 1994

A cDNA encoding a human IL-12R subunit was isolated by expression cloning. This subunit is a 662 amino acid type I transmembrane protein with an extracellular domain of 516 amino acids and a cytoplasmic domain of 91 amino acids. It is a member of the hemopoietin receptor superfamily and is most closely related over its entire length to gp130 and the receptors for granulocyte-CSF (G-CSF) and leukemia-inhibitory factor. When expressed in COS cells, this IL-12R subunit binds both human and murine IL-12 with an apparent affinity of 2 to 5 nM. The transfected COS cells express both monomers and disulfide-linked dimers or oligomers of the IL-12R subunit on their surface. However, unlike the IL-6-induced dimerization of gp130, the oligomerization of the IL-12R subunit is not dependent on binding of IL-12. Only the IL-12R subunit dimers/oligomers but not the monomers bind IL-12 with an affinity of 2 to 5 nM. A polyclonal antiserum raised against this receptor subunit specifically inhibits IL-12-induced proliferation of PHA-activated PBMC. The data are consistent with the hypotheses that 1) a dimer/oligomer of the cloned IL-12R subunit (IL-12R-beta) represents the low affinity IL-12 binding site identified on human lymphoblasts, 2) the cloned receptor subunit is involved in IL-12 signal transduction, and 3) an additional, as of yet unidentified subunit is required to generate a high affinity IL-12R complex.

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1. D. Cua
2. R. Kastelein
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4. C. Langrish
5. Brent S. McKenzie
6. T. Hoey
7. T. Hirano
8. N. Wilson

Citations in the corpus

• IL‐12 and IL‐23: master regulators of innate and adaptive immunity (2004, background): “The high-affinity IL-12 receptor complex is comprised of an IL-12Rb1 and IL-12Rb2 subunit (10, 11).”
• Structural organization of a full-length gp130/LIF-R cytokine receptor transmembrane complex (2008, background): “For the IL-12 cytokine receptor complex, IL-12Rb1 (lacking IgD) interacts with site 2 on the p35 subunit of the IL-12 heterodimer, while IL12Rb2 (contains IgD) interacts with site 3.”
• Stat4 Regulates Multiple Components of IFN-γ-Inducing Signaling Pathways1 (2000, background): “These receptor subunits cooperate in IL-12 binding and signaling, with each chain sharing homology with b-chains of the gp130 family of receptors (2, 3).”
• The biology of IL-12: coordinating innate and adaptive immune responses. (2003, background): “[53] Chua AO, et al.”
• The p38 Mitogen-Activated Protein Kinase Is Required for IL-12-Induced IFN-γ Expression1 (2000, background): “The IL-12R b1-chain, which contains no tyrosine residues in its cytoplasmic domain, interacts with Tyk2 (8, 11).”
• IL-6 in inflammation, autoimmunity and cancer (2020, background): “Additionally, IL-12 acts through IL-12R, which is closely related to gp130 (94).”