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Cutting Edge |
*
Ludwig Institute for Cancer Research, Brussels Branch, and the Experimental Medicine Unit, Christian de Duve Institute of Cellular Pathology, Université de Louvain, Brussels, Belgium; and
Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry, New Jersey Medical School, Newark, NJ 07103.
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-20R
and DIRS1/IL-20R
(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/IL20R (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.
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