Sequence specificity in the recognition of the epidermal growth factor receptor by the abl Src homology 2 domain

The transforming activity of the abl gene product requires a functional src homology 2 (SH2) domain. An assay was developed to evaluate this function by examining binding of a bacteriaUy-expressed abl SH2 domain to the activated EGF receptor, used as a surrogate tyrosine phosphorylated protein. The sequence specificity of this interaction has been explored with a series of point mutants of EGF receptor. Analysis of equilibrium binding reveals that substitution of Tyr 1086 for Phe in the EGF receptor produced a 10-fold reduced affinity for abl SH2 domain binding as compared to the wildtype receptor