Identification and functional characterization of a second chain of the interleukin-10 receptor complex.
Interleukin-10 (IL-10) is a pleiotropic cytokine which signals through a specific cell surface receptor complex. Only one chain, that for ligand binding (IL-10Ralpha or IL-10R1), was identified previously. We report here that, although human IL-10 binds to the human IL-10R1 chain expressed in hamster cells, it does not induce signal transduction. However, the co-expression of CRFB4, a transmembrane protein of previously unknown function belonging to the class II cytokine receptor family, together with the IL-10R1 chain renders hamster cells sensitive to IL-10. The IL-10:CRFB4 complex was detected by cross-linking to labeled IL-10. In addition, the IL-10R1 chain was able to be co-immunoprecipitated with anti-CRF antibody when peripheral blood mononuclear cells were treated with IL-10. These results demonstrate that the CRFB4 chain is part of the IL-10 receptor signaling complex. Thus, the CRFB4 chain, which we designate as the IL-10R2 or IL-10Rbeta chain, serves as an accessory chain essential for the active IL-10 receptor complex and to initiate IL-10-induced signal transduction events.
Kotenko
S V
SV
Department of Molecular Genetics and Microbiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854-5635, USA.
Krause
C D
CD
Izotova
L S
LS
Pollack
B P
BP
Wu
W
W
Pestka
S
S
D000818:Animals; D019556:COS Cells; D006224:Cricetinae; D003432:Cross-Linking Reagents / Q000494:pharmacology; D000882:Haplorhini; D006801:Humans; D053710:Interleukin-10 Receptor beta Subunit; D053613:Janus Kinase 1; D008562:Membrane Glycoproteins; D009000:Monocytes / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D018121:Receptors, Cytokine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053701:Receptors, Interleukin-10; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013388:Succinimides / Q000494:pharmacology; D053634:TYK2 Kinase
D003432:Cross-Linking Reagents; C081846:IL10RB protein, human; D053710:Interleukin-10 Receptor beta Subunit; D008562:Membrane Glycoproteins; D011506:Proteins; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D011993:Recombinant Fusion Proteins; D013388:Succinimides; C035759:3,3'-dithiobis(sulfosuccinimidyl propionate); D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1; D053634:TYK2 Kinase; C070139:TYK2 protein, human