ABSTRACT

As the sequences of many protein-tyrosine kinases have been determined by analysis of cDNA clones, it has become clear that most protein-tyrosine kinases fall into groups. Most, probably all, of the src family genes have the potential to mutate into oncogenes—that is, dominant alleles that cause malignant transformation. Indeed, the first genetic demonstration of an oncogene made use of Rous sarcoma virus, which carries an oncogenic form of c-src known as viral (v)-src. Almost entire knowledge of src family kinase structure is based on their cDNA sequences and radiolabeling studies. None of the proteins has been obtained in sufficient quantity to permit the sorts of analyses that reveal details of three-dimensional structure. The src family genes appear to lack transforming activity, even when overex-pressed, but are prone to oncogenic mutations. Despite considerable progress in understanding regulation, mapping mutants, and cataloging substrates of src family kinases, as yet no member of the family has a firmly ascribable biological function.