Human Interleukin 20 Receptor Subunits

Figure 1. IL-20 signals through a heterodimeric complex, consisting of IL-20 R alpha and IL-20 R beta. Binding of recombinant IL-20 induces signal transduction through STAT3.

IL-20, an IL-10-like cytokine, signals through a heterodimeric complex consisting of IL-20 R alpha (previously designated zcytor7 and CRF2-8) and a second component IL-20 R beta (originally named DIRS1). Both subunits are class II cytokine receptors containing two fibronectin type III domains and a tissue factor-like domain in the extracellular region. Soluble IL-20 R alpha has six potential N-linked glycosylation sites while soluble IL-20 R beta has three potential N-linked glycosylation sites. Both subunits are required for IL-20 binding as demonstrated by the fact that transfected cells expressing either receptor subunit alone show no detectable binding to IL-20.^1-5 The requirement of both receptor subunits for IL-20 binding distinguishes their role from that of the subunits of the four other known class II cytokine receptors. For example, in the IL-10 heterodimeric receptor, the IL-10 R alpha subunit is sufficient for high affinity binding of IL-10, while IL-10 R beta is responsible for signaling. The binding of recombinant IL-20 to the hetero-dimeric receptor induces signal transduction through STAT3, as does the binding of IL-10 to its receptor complex. IL-10, however, may also activate STAT1 to some extent, which has not been observed with IL-20.

IL-20 R alpha and IL-20 R beta are expressed in a variety of tissues. IL-20 R alpha appears to be more widely expressed than IL-20 R beta, suggesting that IL-20 R alpha may partner with other class II cytokine receptors. RT-PCR analyses reveal that IL-20 R alpha is most abundant in skin, testis, prostate, placenta, and heart.⁴ Lower amounts of IL-20 R alpha RNA are found in brain, lung, stomach, pancreas, thyroid, ovary, adrenal gland, uterus, and salivary gland. No IL-20 R alpha RNA is detected in kidney, spleen, liver, colon, muscle, peripheral blood lymphocytes, or bone marrow. IL-20 R beta is expressed in several tissues and is most abundant in skin, testis, and ovary.⁴ Lower amounts of IL-20 R beta RNA are found in placenta, lung, stomach, and brain.

References

1. Lok, S. et al. (1999) U. S. Patent 5,945,511.
2. Kotenko, S. and S. Pestka (2000) Oncogene 19:2557.
3. Lok, S. et al. (1999) U. S. Patent 5,965704.
4. Blumberg, H. et al. (2001) Cell 104:9.
5. Parham, C. et al. (1999) International Patent Application WO/99/46379.