Rapid identification of proteins that interact with a novel gene product is
an important element of functional genomics. Here we describe a phage disp
lay-based technique for interaction screening of complex cDNA libraries usi
ng proteins or synthetic peptides as baits. Starting with the epidermal gro
wth factor receptor (EGFR) cytoplasmic tail, we identified known protein in
teractions that link EGFR to the Ras/MAP kinase signal transduction cascade
and several novel interactions. This approach can be used as a rapid and e
fficient tool for elucidating protein networks and mapping intracellular si
gnal transduction pathways.