ONCOGENIC ACTIVATION OF C-ABL BY MUTATION WITHIN ITS LAST EXON

被引:54
作者
GOGA, A
MCLAUGHLIN, J
PENDERGAST, AM
PARMAR, K
MULLER, A
ROSENBERG, N
WITTE, ON
机构
[1] UNIV CALIF LOS ANGELES, DEPT MICROBIOL & MOLEC GENET, LOS ANGELES, CA 90024 USA
[2] TUFTS UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02111 USA
[3] TUFTS UNIV, SCH MED, DEPT MOLEC BIOL & MICROBIOL, BOSTON, MA 02111 USA
[4] UNIV CALIF LOS ANGELES, HOWARD HUGHES MED INST, LOS ANGELES, CA 90024 USA
[5] UNIV CALIF LOS ANGELES, INST MOLEC BIOL, LOS ANGELES, CA 90024 USA
关键词
D O I
10.1128/MCB.13.8.4967
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The c-ABL proto-oncogene is 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.
引用
收藏
页码:4967 / 4975
页数:9
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