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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
24
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pubmed:dateCreated |
1997-1-16
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pubmed:databankReference |
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pubmed:abstractText |
We have identified a cDNA from a human phytohemagglutinin-activated lymphoblast library encoding a protein that binds 125I-labeled human interleukin 12 (125I-huIL-12) with a Kd of about 5 nM when expressed in COS-7 cells. When coexpressed in COS-7 cells with the previously identified IL-12 beta receptor (IL-12R beta) protein, two classes of 125I-huIL-12 binding sites were measured with Kds of about 55 pM and 8 nM, corresponding to the high- and low-affinity binding sites seen on phytohemagglutinin-activated lymphoblasts. This newly identified huIL-12R subunit is a member of the cytokine receptor superfamily, with closest resemblance to the beta-type cytokine receptor gp130 and the receptors for leukemia inhibitory factor and granulocyte colony-stimulating factor. Consequently, we have reclassified the previously identified IL-12R beta subunit as huIL-12R beta 1 and designated the newly identified subunit as huIL-12R beta 2. huIL-12R beta 2 is an 862-amino acid type I transmembrane protein with a 595-amino-acid-long extracellular domain and a cytoplasmic tail of 216 amino acids that contains three tyrosine residues. A cDNA encoding the mouse homolog of the huIL12R beta 2 protein has also been isolated. Human and mouse IL-12R beta 2 proteins show a 68% amino acid sequence identity. When expressed in COS-7 cells, huIL-12R beta 2 exists as a disulfide-linked oligomer with an apparent monomeric molecular weight of 130 kDa. Coexpression of the two identified IL-12R subunits in Ba/F3 cells conferred IL-12 responsiveness, and clones of these cotransfected Ba/F3 cells that grew continuously in the presence of IL-12 were isolated and designated LJM-1 cells. LJM-1 cells exhibited dose-dependent proliferation in response to huIL-12, with an ED50 of about 1 pM huIL-12. Interestingly, Ba/F3 cells transfected with IL-12R beta 2 alone proliferated in response to huIL-12 with an ED50 of about 50 pM, although a role for endogenous mouse IL-12R beta 1 in IL-12 signal transduction in these transfectants cannot be ruled out. These results demonstrate that the functional high-affinity IL-12R is composed of at least two beta-type cytokine receptor subunits, each independently exhibiting a low affinity for IL-12.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-1578138,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-1578139,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-1582416,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-1672545,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-1673147,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-1698283,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-1713608,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-1715362,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-1828890,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-2163696,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-2204066,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-2504877,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-3371661,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-3840547,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-3924409,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-6855599,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-7516409,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-7809096,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-7843232,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-7908534,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-7911493,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-7994020,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-8096238,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-8097338,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-8248239,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-8378320,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-8395346,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-8552611,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-8594314,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-8617302,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-8630732,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8943050-8839143
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
26
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pubmed:volume |
93
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
14002-7
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:8943050-Amino Acid Sequence,
pubmed-meshheading:8943050-Animals,
pubmed-meshheading:8943050-Binding Sites,
pubmed-meshheading:8943050-COS Cells,
pubmed-meshheading:8943050-Cell Membrane,
pubmed-meshheading:8943050-Cells, Cultured,
pubmed-meshheading:8943050-Cloning, Molecular,
pubmed-meshheading:8943050-Humans,
pubmed-meshheading:8943050-Interleukin-12,
pubmed-meshheading:8943050-Macromolecular Substances,
pubmed-meshheading:8943050-Mice,
pubmed-meshheading:8943050-Molecular Sequence Data,
pubmed-meshheading:8943050-Receptors, Cytokine,
pubmed-meshheading:8943050-Receptors, Interleukin,
pubmed-meshheading:8943050-Receptors, Interleukin-12,
pubmed-meshheading:8943050-Recombinant Proteins,
pubmed-meshheading:8943050-Sequence Homology, Amino Acid,
pubmed-meshheading:8943050-Transfection
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pubmed:year |
1996
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pubmed:articleTitle |
A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits.
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pubmed:affiliation |
Department of Inflammation/Autoimmune Diseases, Hoffmann-La Roche, Inc., Nutley, NJ 07110, USA.
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pubmed:publicationType |
Journal Article
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