Identification of receptor tyrosine kinase (RTK) substrates by the cloning of receptor targets (CORT) strategy

Activation of receptor tyrosine kinases (RTXs) leads to autophosphorylation of the intracellular region of the receptor on specific tyrosine residues, thus creating binding sites for a variety of signaling proteins (1). These interactions are mediated by protein modules such as src homology (SH)2 and phosphotyrosine binding (PTB) domains, which target specific tyrosine phosphorylated peptide sequences (2). This chapter describes how the physical association of an RTK with particular substrates can be exploited in an expression cloning procedure and novel receptor targets identified.