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

Journal Article · Fri Jul 01 00:00:00 EDT 1994 · Journal of Immunology; (United States)

OSTI ID:6652047

Chua, A O; Chizzonite, R; Desai, B B; Truitt, T P; Nunes, P; Minetti, L J; Warrier, R R; Presky, D H; Levine, J F; Gately, M K ^[1]

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1. Roche Research Center, Nutley, NJ (United States); and others

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 4 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 hypothesis that (1) a dimer/oligomer of the cloned IL-12R subunit (IL-2R-[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. 40 refs., 6 figs.

• OSTI ID: 6652047
• Journal Information: Journal of Immunology; (United States), Vol. 153:1; ISSN 0022-1767
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GENES
DNA-CLONING
MEMBRANE PROTEINS
RECEPTORS
AMINO ACID SEQUENCE
DNA SEQUENCING
BIOTECHNOLOGY
CLONING
DNA HYBRIDIZATION
GENETIC ENGINEERING
HYBRIDIZATION
MOLECULAR STRUCTURE
NUCLEIC ACID HYBRIDIZATION
ORGANIC COMPOUNDS
PROTEINS
STRUCTURAL CHEMICAL ANALYSIS
550400* - Genetics