Date of Award
Doctor of Philosophy (PhD)
Avian sarcoma virus UR2 is a replication-defective virus that can induce sarcomas in vivo and transforms chicken embryo fibroblasts in culture to a characteristic, extremely elongated morphology. The genome of UR2 contains a 1.2 kb transformation-specific sequence, v-ros, which has a homologous counterpart, cros, in normal chicken cellular DNA. The 5' end of v-ros is fused to the helper virus UR2AV-related sequencing coding for one of the viral gag proteins, p19. The fused p19 and ros sequences in UR2 code for a polyprotein of 68 kd, P68gag-ros, which has an associated tyrosine kinase activity. To elucidate the basis of the functional conservation as well as differences between ros and other oncogenes, I sequenced the entire genome of UR2 and compared the predicted amino acid sequence of P68 with other members of the tyrosine kinase family. The results show that ros is 1273 nucleotides in length, including a 65 bp 3' noncoding stretch. ros is joined at its 5' and 3' ends to the 3' region of p19, and the 3' region of gp37, respectively, and replaces the sequences of UR2AV in between. The deduced amino acid sequence for P68 gives a molecular weight of 61,113 daltons and shows that it is closely related to the oncogene family coding for tyrosine protein kinases. However, P68 contains two distinctive hydrophobic regions that are absent in most of the other tyrosine kinases and it has unique amino acid changes and insertions within the conserved domain of the kinases. I also determined the sequence of cellular ros and compared it to viral ros to determine the changes between them that may be responsible for their differential oncogenicity; in addition I have analysed the expression of the cellular gene in both embryonic and adult chickens. The 1.2 kb v-ros sequence is remarkably well conserved when compared with the corresponding region of c-ros. The v-ros sequences are distributed in nine exons of c-ros over a. range of 12 kb of DNA.
Neckameyer, Wendi S., "The Oncogene of Avian Sarcoma Virus UR2 and its Cellular Homologue: Structure, Sequence and Expression" (1985). Student Theses and Dissertations. 463.