We have previously described the initial characterization of a novel human gene closely related to the abl oncogene. In order to understand the function of this gene, termed arg, we have now identified and characterized c-DNA clones of its transcript. The overall structure of the arg transcript is unusual in that the coding sequence is located at the 5' extremity, and at least 5.5 kb of the noncoding sequence is located at the 3' end. The complete coding sequence of the gene has been deduced from the large open reading frame located at the 5' of the transcript. Comparison of its amino acid structure with that of abl has revealed several interesting differences and similarities. Of note is the finding that the arg transcript is composed of alternative first exons that allow the translation of two arg proteins that differ only at their N-termini. This was a particularly surprising finding because only one arg transcript can be identified in northern blot analysis. Clones containing the complete arg coding sequence have been assembled in appropriate mammalian expression vectors. Additionally a gag-arg construct analagous to v-abl has been engineered. These clones will allow an initial investigation of the biology of arg using the NIH/3T3 focus forming assay system. In addition to information pertaining to the transforming capability of arg, cell lines containing the normal arg expression vectors will allow the determination of the subcellular localization of the arg protein. Arg expression vectors will also be introduced into hematopoietic cells to determine if arg has the lymphocytic specificity that v-abl displays. In addition to the in vitro characterization of arg, viruses derived from the cell lines described above will be introduced into mice. These experiments will allow the in vivo tumorigenic properties of arg to be evaluated.
