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Publication : Activation of murine c-abl protooncogene: effect of a point mutation on oncogenic activation.

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.
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