Activation of tyrosine kinase growth factor receptors leads to autophosphorylation of specific tyrosine residues within the intracellular region of the receptor. The phosphorylated tyrosines serve as binding sites for various cytoplasmic proteins. The Shc protein is one such protein. Upon activation of the chicken c-erbB protein by ligand Shc binds to the c-erbB protein and becomes phosphorylated on tyrosine. Similarly, Shc is found bound to the constitutively phosphorylated v-erbB protein encoded by the avian erythroblastosis virus strain H, AEV-H. Utilizing various mutant forms of the v-erbB protein, the residue equivalent to tyrosine 1154 in the chicken c-erbB protein was shown to serve as a binding site for the Shc protein to the AEV-H v-erbB protein. However, binding to this site was not essential for transformation since v-erbB oncoproteins which lacked this site still transform both erythroid cells and fibroblasts.