Cutting edge: STAT activation by IL-19, IL-20 and mda-7 through IL-20 receptor complexes of two types.
IL-10-related cytokines include IL-20 and IL-22, which induce, respectively, keratinocyte proliferation and acute phase production by hepatocytes, as well as IL-19, melanoma differentiation-associated gene 7, and AK155, three cytokines for which no activity nor receptor complex has been described thus far. Here, we show that mda-7 and IL-19 bind to the previously described IL-20R complex, composed by cytokine receptor family 2-8/IL-20Ralpha and DIRS1/IL-20Rbeta (type I IL-20R). In addition, mda-7 and IL-20, but not IL-19, bind to another receptor complex, composed by IL-22R and DIRS1/IL20Rbeta (type II IL-20R). In both cases, binding of the ligands results in STAT3 phosphorylation and activation of a minimal promoter including STAT-binding sites. Taken together, these results demonstrate that: 1) IL-20 induces STAT activation through IL-20R complexes of two types; 2) mda-7 and IL-20 redundantly signal through both complexes; and 3) IL-19 signals only through the type I IL-20R complex.
Dumoutier
L
L
Ludwig Institute for Cancer Research, Brussels Branch, Avenue Hippocrate 74, B-1200 Brussels, Belgium.
Leemans
C
C
Lejeune
D
D
Kotenko
S V
SV
Renauld
J C
JC
D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D017930:Genes, Reporter; D016147:Genes, Tumor Suppressor; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology*; D046911:Macromolecular Substances; D008954:Models, Biological; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D000097043:Interleukin-22; D000099180:Interleukin-24
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006133:Growth Substances; D016753:Interleukin-10; D007378:Interleukins; D046911:Macromolecular Substances; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D000097043:Interleukin-22; D000099180:Interleukin-24; C421250:IL19 protein, human; C433253:IL22RA2 protein, human; C494086:STAT3 protein, human; C415369:interleukin-22 receptor; C422042:interleukin 20