Method for identifying a substance which mediates interaction between interleukin 22 and an interleukin 22 receptor
Interleukin-22 interacts with its receptor, referred to as IL-22R, and instigates a series of reactions, leading to activation of various molecules, such as JAK-1, Tyk2, and others. One can identify molecules which mediate this interaction by measuring the activity of one or more of the molecules in the pathway, to identify agonists and antagonists. These, in turn, are useful therapeutic agents, where inappropriate expression of one of the activated molecules is at issue, and requires amelioration.
1. A method for identifying a substance which mediates binding between interleukin-22 (IL-22) and an interleukin-22 receptor (IL-22R), comprising:
a) admixing IL-22 or an IL-22R binding fragment thereof, a cell which presents an IL-22R or an IL-22 binding fragment thereof on its surface, and said substance,
b) determining activation of a molecule that is expressed by said cell, said molecule selected from the group consisting of STAT1, STAT5, JAK-1, Tyk2, ERK1/2, MEK1/2, p90RSK, JNK/SAPR and p38, and
c) comparing activation of said molecule to activation when said cell is admixed with IL-22 or an IL-22R binding fragment thereof in the absence of said substance, any differences therebetween indicating said substance mediates said binding.
2. The method of claim 1 , comprising determining said activation via an immunoassay.
3. The method of claim 1 , comprising determining said activation via measuring nucleic acid expression of said molecule.
4. The method of claim 2 , wherein said immunoassay comprises an assay using an antibody which binds specifically to a phosphorylated form of said molecule.
5. The method of claim 1 , comprising determining said expression via a hybridization assay.
6. The method of claim 3 , comprising determining said activation by transfecting or transforming said cell with a nucleic acid molecule which generates a detectable signal upon activation of said molecule selected from the group consisting of STAT1, STAT5, JAK-1, Tyk2, ERK1/2, MEK1/2, p90RSK. JNK/SAPR and p38.