Method for determining cytokine receptor activation by the use of an antibody

Abstract

The present invention relates to a method for determinating cytokine receptor, especially growth hormone receptor (GHR), activation, by the use of an antibody capable of discrimating between an activated and an inactive cytokine receptor conformation, especially GHR or growth hormone binding protein (GHBP) conformation, the method comprising: contacting the antibody and the cytokine receptor to form a complex, contacting a candidate ligand to the complex, measuring the antibody binding to inactive cytokine receptor and thereby discriminating between an activated and an inactive conformation. It also relates to a method for screening for functionally cytokine agonists and antagonists, especially functionally growth hormone (GH) agonists, among candidate ligands by the use of an antibody specific for activated cytokine receptor conformation. The invention also relates to an antibody directed to the hinge spanning subdomains I and II of the growth hormone receptor extracellular region and which is capable of discriminating between an activated and an inactive receptor conformation. The invention also relates to the use of the antibody for e.g. characterization of growth hormone receptor interactions and for screening for compounds stabilising the dimerization of GHR.