Patent ID: 6884598

Claim:
A method for screening for a molecule that agonizes or antagonizes RANK activity in cells expressing RANK, wherein RANK is a polypeptide that is capable of activating NF-κB and that is selected from the group consisting of: i) amino acids 1-616 of SEQ ID NO:2; ii) amino acids 1-625 of SEQ ID NO:4; and iii) a polypeptide having an at least 90% amino acid sequence identity with (i) or (ii), said method comprising the steps of: (a) contacting a candidate molecule with cells expressing RANK, said RANK expressing cells comprising a nucleic acid molecule encoding a reporter protein, said nucleic acid molecule being operably linked to a RANK-responsive regulatory nucleic acid sequence that is selected from the group consisting of a human or murine MMP-9 promoter and a human or murine TRAP promoter, wherein the cells are exposed to a RANK trigger prior to, during or after being contacted with said candidate molecule; (b) determining whether the level of reporter molecule expression in the contacted cells is enhanced or reduced as compared with the level of reporter molecule expression in a culture of reference RANK expressing cells that are not contacted with the candidate molecule; and (c) identifying the candidate molecule as a RANK agonist if the level of reporter molecule expression in the contacted cells is comparatively enhanced and identifying the candidate molecule as an RANK antagonist if the level of reporter molecule expression in the contacted cells is comparatively reduced.