First Author | Shore SK | Year | 1990 |
Journal | Proc Natl Acad Sci U S A | Volume | 87 |
Issue | 17 | Pages | 6502-6 |
PubMed ID | 2168550 | Mgi Jnum | J:14646 |
Mgi Id | MGI:62810 | Doi | 10.1073/pnas.87.17.6502 |
Citation | Shore SK, et al. (1990) Activation of murine c-abl protooncogene: effect of a point mutation on oncogenic activation. Proc Natl Acad Sci U S A 87(17):6502-6 |
abstractText | Activation of the c-abl protooncogene occurs in Abelson murine leukemia virus, in Hardy-Zuckerman 2 feline sarcoma virus, and during the chromosomal translocations that generate BCR-ABL gene fusion products. To study the molecular mechanism involved in the c-abl activation, we have created a series of modifications in murine c-abl and assayed these constructs for oncogenic activity using the NIH 3T3 cell transformation assay. Our results show that amino-terminal deletions are sufficient for oncogenic activation of c-abl and high levels of oncogenic activities were generated by a deletion of 114 codons from the 5' end that deleted the SH3 region. A deletion of 53 codons from the 5' end (inclusive of deletions seen in Hardy-Zuckerman 2 feline sarcoma virus and BCR-ABL gene products) that retains the SH3 region of c-abl resulted in the generation of low levels of transforming activity. This transforming potential was substantially increased with the introduction of a G----A point mutation in codon 832 that is present in v-abl. The point mutation was found to affect the secondary structure and the tyrosine kinase activity of the mutant gene products. |