Open AccessThe Bcr-Abl leukemia oncogene activates Jun kinase and requires Jun for transformation.
Author(s) -
Arthur Raitano,
Jocelyn R. Halpern,
Tina Hambuch,
Charles L. Sawyers
Publication year - 1995
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.92.25.11746
Subject(s) - mitogen activated protein kinase kinase , cancer research , map kinase kinase kinase , ask1 , mapk/erk pathway , abl , mitogen activated protein kinase 3 , cyclin dependent kinase 9 , c raf , microbiology and biotechnology , tyrosine kinase , map2k7 , biology , kinase , breakpoint cluster region , signal transduction , cyclin dependent kinase 2 , protein kinase a , biochemistry , receptor
The leukemogenic tyrosine kinase fusion protein Bcr-Abl activates a Ras-dependent pathway required for transformation. To examine subsequent signal transduction events we measured the effect of Bcr-Abl on two mitogen-activated protein kinase (MAPK) cascades--the extracellular signal-regulated kinase (ERK) pathway and the Jun N-terminal kinase (JNK) pathway. We find that Bcr-Abl primarily activates JNK in fibroblasts and hematopoietic cells. Bcr-Abl enhances JNK function as measured by transcription from Jun responsive promoters and requires Ras, MEK kinase (MAPK/ERK kinase kinase), and JNK to do so. Dominant-negative mutants of c-Jun, which inhibit the endpoint of the JNK pathway, impair Bcr-Abl transforming activity. These findings implicate the JNK pathway in transformation by a human leukemia oncogene.