Activation of murine c-abl protooncogene: effect of a point mutation on oncogenic activation.
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.
Shore
S K
SK
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104-4268.
Bogart
S L
SL
Reddy
E P
EP
D000011:Abelson murine leukemia virus / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002872:Chromosome Deletion; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D009052:Leukemia Virus, Murine / Q000235:genetics*; D051379:Mice; D009154:Mutation; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016315:Proto-Oncogene Proteins c-abl; D011519:Proto-Oncogenes; D014162:Transfection
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl