Oncogenic activation of c-ABL by mutation within its last exon.

Journal Article

The c-ABL proto-oncogene is a predominantly nuclear localized tyrosine kinase. A random mutagenesis scheme was used to isolate c-ABL mutants whose expression produced a transformed phenotype in rodent fibroblast cells. An in-frame deletion within the central region of the last exon was identified in one ABL mutant. The mechanism of c-ABL oncogenic activation by mutation within the last exon differs both functionally and structurally from those of v-ABL and BCR/ABL. This class of ABL mutants shows increased tyrosine phosphorylation of cellular proteins in vivo but low levels of autophosphorylation. Last-exon ABL mutants are distinguished from v-ABL or BCR/ABL by their inability to transform primary bone marrow cells or support the growth of transformed pre-B cells. These findings define a new mechanism of oncogenic activation for the ABL kinase through mutations in the last exon which do not require amino-terminal deletions or mutations within the src homology regions.

Full Text

Duke Authors

Cited Authors

  • Goga, A; McLaughlin, J; Pendergast, AM; Parmar, K; Muller, A; Rosenberg, N; Witte, ON

Published Date

  • August 1993

Published In

Volume / Issue

  • 13 / 8

Start / End Page

  • 4967 - 4975

PubMed ID

  • 8336729

International Standard Serial Number (ISSN)

  • 0270-7306

Language

  • eng

Conference Location

  • United States