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

Content Provider	Semantic Scholar
Author	Shore, Scott K. Bogart, Stephanie L. Reddy, E. P.
Copyright Year	1990
Abstract	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.
File Format	PDF HTM / HTML
DOI	10.1073/pnas.87.17.6502
PubMed reference number	2168550
Journal	Medline
Volume Number	87
Issue Number	17
Alternate Webpage(s)	http://www.pnas.org/content/87/17/6502.full.pdf
Alternate Webpage(s)	https://doi.org/10.1073/pnas.87.17.6502
Journal	Proceedings of the National Academy of Sciences of the United States of America
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article