Expression cloning of a human IL-12 receptor component. A new member of the cytokine receptor superfamily with strong homology to gp130.
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.
Chua
A O
AO
Department of Inflammation/Autoimmune Diseases, Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Chizzonite
R
R
Desai
B B
BB
Truitt
T P
TP
Nunes
P
P
Minetti
L J
LJ
Warrier
R R
RR
Presky
D H
DH
Levine
J F
JF
Gately
M K
MK
D000595:Amino Acid Sequence; D015703:Antigens, CD; D003001:Cloning, Molecular; D016384:Consensus Sequence; D050822:Cytokine Receptor gp130; D018076:DNA, Complementary / Q000235:genetics; D005796:Genes; D006801:Humans; D018664:Interleukin-12; D007378:Interleukins / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry; D008969:Molecular Sequence Data; D005810:Multigene Family; D018121:Receptors, Cytokine / Q000235:genetics*; D018123:Receptors, Interleukin / Q000235:genetics*; D053707:Receptors, Interleukin-12; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D015703:Antigens, CD; D018076:DNA, Complementary; C494199:IL6ST protein, human; D007378:Interleukins; D008562:Membrane Glycoproteins; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D050822:Cytokine Receptor gp130; D018664:Interleukin-12