Methods for preparing polynucleotides encoding orphan receptor ligands

A method for preparing polynucleotide molecules wherein at least one of said molecules encodes a ligand for an orphan growth factor receptor comprising:

• (a) providing parent cells, wherein growth of said cells is dependent upon an exogenous growth factor;
• (b) transfecting said parent cells with a DNA construct encoding an orphan growth factor receptor to produce transfected cells expressing said orphan growth factor receptor encoded by said DNA construct;
• (c) exposing said transfected cells to mutagenizing conditions to produce mutagenized cells;
• (d) culturing said mutagenized cells under conditions in which cell survival is dependent upon autocrine growth factor production;
• (e) recovering progeny cells that survive said culturing step;
• (f) screening said progeny cells to identify cells that produce a ligand for said orphan growth factor receptor;
• and
• (g) preparing polynucleotide molecules from said identified cells wherein at least one of said molecules encodes said ligand.