Influence of acidic residues on substrate specificity of oncogene products pp60(v-src) and p56(lck) in vitro

Substrate specificities of two protein tyrosine kinases were compared using nine undecapeptides modeled after human gastrin. Using the proto-oncogene product, p56(lck), V(max) decreased with the distance between glutamate and tyrosine, whereas for the oncogene product, pp60(v-src) there was no relation. For pp60(v-src) there was a precipitous rise in K(m), from 2.9 to 20 mM when glutamate was more than 3 residues away from tyrosine. For p56(lck), K(m) was a minimum when glutamate occupied either a position 3 residues, or both positions 3 and 4, N-terminal to tyrosine. An important factor in enzyme recognition of these peptides is glutamate three residues N-terminal to tyrosine.