Methods of identifying negative antagonists for G protein coupled receptors

摘要

The present invention is directed to a constitutively active G protein coupled receptor of human herpesvirus 8, as well as a method of identifying negative antagonists of a constitutively active G protein coupled receptor. The method comprises co-expressing in a host cell a constitutively active G protein coupled receptor and a reporter protein, wherein expression of the reporter protein is controlled by a promoter responsive to a signalling pathway activated by the constitutively active G protein coupled receptor; exposing the host cell to a test substance; and determining a level of reporter protein activity, wherein the level of reporter protein activity indicates effectiveness of the test substance as a negative antagonist of the constitutively active G protein coupled receptor. The invention further provides a method of preventing tumor formation or cell proliferation caused by a constitutively active G protein coupled receptor. This method comprises administering an amount of the negative antagonist so identified to a subject in an amount effective to prevent tumor formation or cell proliferation.