The entire coding sequence of dbl proto-oncogene was determined. The sequence analysis revealed that dbl proto- oncogene codes for a 925-amino acid protein. It is a hydrophilic protein with a characteristic alpha-helical coiled-coil structure similar to that of intermediate filaments. The dbl proto-oncogene sequence showed no homology to any known oncogene and thus may represent a member of a new class of oncogenes. Comparison of the proto-oncogene sequence with that of the activated dbl revealed that the transforming gene was rearranged with respect to its amino-terminal domain. The oncogenic potential of the dbl proto-oncogene was examined by cloning the full length cDNA in several eukaryotic expression vectors and transfecting these vectors to NIH/3T3 cells. These studies showed that the dbl proto-oncogene is capable of transforming NIH/3T3 cells when it is driven by a strong promoter. However, this activity was lower than that found with the activated dbl driven by the same promoter. The dbl proto-oncogene product was detected for the first time utilizing the COS cell system and an expression vector driven by SV40 early promoter. The size of the dbl proto-oncogene protein was determined to be approximately 110 kd.
