THE BCR-ABL LEUKEMIA ONCOGENE ACTIVATES JUN KINASE AND REQUIRES JUN FOR TRANSFORMATION

被引:360
作者
RAITANO, AB
HALPERN, JR
HAMBUCH, TM
SAWYERS, CL
机构
[1] UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, DIV HEMATOL ONCOL, LOS ANGELES, CA 90095 USA
[2] UNIV CALIF LOS ANGELES, SCH MED, INST MOLEC BIOL, LOS ANGELES, CA 90095 USA
关键词
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.
引用
收藏
页码:11746 / 11750
页数:5
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