Structural features of the carboxy terminus of p60c-src that are required for the regulation of its intrinsic kinase activity.

The major structural difference between p60c-src and p60v-src resides in the carboxy-terminal region. We introduced substitution, replacement and deletion into the carboxy-terminal region of chicken p60c-src and examined the effects on its biochemical and biological properties in chicken embryo fibroblasts. The replacement of the carboxy-terminal region after amino acid position 515 of p60c-src with the corresponding region of p60v-src converted p60c-src to a transforming protein with elevated kinase activity. The substitution of Tyr527, which is a major tyrosine phosphorylation site of p60c-src, with phenylalanine resulted in an increase of kinase activity and in transforming ability. On the other hand, a deletion after position 515 abolished the kinase activity. These results revealed the structural features of the carboxy terminus of p60c-src that are required for the regulation of its intrinsic protein kinase activity.