CHRONIC MYELOGENOUS LEUKEMIA;
MITOGEN-ACTIVATED PROTEIN KINASE;
D O I:
10.1073/pnas.92.25.11746
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
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 JNL 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.