The Bcr-Abl leukemia oncogene activates Jun kinase and requires Jun for transformation. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • December 5, 1995

Research

keywords

  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cell Transformation, Neoplastic
  • Fusion Proteins, bcr-abl
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • MAP Kinase Kinase Kinase 1
  • Mitogen-Activated Protein Kinases
  • Oncogenes
  • Proto-Oncogene Proteins c-jun

Identity

PubMed Central ID

  • PMC40479

Scopus Document Identifier

  • 0029589929

Digital Object Identifier (DOI)

  • 10.1073/pnas.92.25.11746

PubMed ID

  • 8524841

Additional Document Info

volume

  • 92

issue

  • 25