The human lck cDNA clone YT16 is a transforming oncogene

The lck gene belongs to the src gene family and it is implicated in processes of lymphomagenesis. A full-:length lck-encoding cDNA clone, termed YT16 was isolated from a subtractive cDNA library, which was specific for expressed genes of the human Jurkat T-cell lymphoma. Sequence analysis of this molecular clone revealed major structural alterations compared to other tyrosine kinases classified as src-related genes. Firstly, a region within thw YT16 sequence surrounding the conserved ATP-binding site was modified by several short frameshift mutations. Secondly, the regulatory important tyrosine-505 residue was substituted by a threonine at this aligned position. The latter mutation was expected to result in a constitutional hypophosphorylated and thus permanently activated protein tyrosine kinase. These significant genetic alterations within the coding region of YT16 prompted us to investigate its biological relevance in vivo. To this end, we expressed YT16-specific sequences in NIH 3T3 fibroblasts and looked for morphological transformation of transfected cells. Here we report, that transformation of NIH 3T3 cells is obtained, provided that inhibitory untranslated sequences are removed from the YT16 cDNA clone. These results lend support to the notion, that structurally altered lck genes, in this study represented by the YT16 clone, may contribute to neoplastic processes in lymphoid cells.