Method for influencing kinase pathways with IL-22

Abstract

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.

We claim:  
     
         1 . A method for identifying a substance which mediates interaction between interleukin-22 (IL-22) and an interleukin -22 receptor (IL-22R), comprising admixing an IL-22 molecule or a receptor binding fragment thereof, a cell which presents an IL-22 receptor or an IL-22 receptor binding fragment thereof on its surface and said compound, determining activation of a molecule that is expressed by said cell, said molecule selected from the group consisting of STAT1, STAT3, STAT5, JAK-1, Tyk2, ERK1/2, MEK1/2, p90RSK, JNK/SAPK and p38, and comparing activation of said molecule to activation when said cell which presents an IL-22R or IL-22 binding fragment thereof is admixed with IL-22 or an IL-22R binding fragment, 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 4 , wherein said antibody binds specifically to phosphorylated serine on STAT3.  
     
     
         6 . The method of  claim 1 , comprising determining said expression via a hybridization assay.  
     
     
         7 . 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.  
     
     
         8 . A method for treating a subject suffering from a condition associated with inappropriate expression of a molecule selected from the group consisting of STAT1, STAT3, STAT5, JAK-1, Tyk2, ERK1/2, MEK1/2, p90RSK, JNK/SAPK and p38, comprising administering to said subject an amount of a mediator of binding between IL-22 and an IL-22R sufficient to ameliorate said inappropriate expression.  
     
     
         9 . A method for treating a subject suffering from a condition associated with inappropriate activity of IL-22 comprising administering to said subject an inhibitor of JAK-1, Tyk2, ERK1, MEK1, p90RSK, JNK or p38 sufficient to inhibit IL-22 activity.