Suppression of Ras-stimulated transformation by the JNK signal transduction pathway

  1. Norman J. Kennedy1,
  2. Hayla K. Sluss2,
  3. Stephen N. Jones2,
  4. Dafna Bar-Sagi3,
  5. Richard A. Flavell4, and
  6. Roger J. Davis1,5
  1. 1Howard Hughes Medical Institute, and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA; 2Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA; 3Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, Stony Brook, New York 11794, USA; 4Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA

Abstract

The c-Jun NH2-terminal kinase (JNK) phosphorylates and activates members of the activator protein-1 (AP-1) group of transcription factors and is implicated in oncogenic transformation. To examine the role of JNK, we investigated the effect of JNK deficiency on Ras-stimulated transformation. We demonstrate that although JNK does play a role in transformation in vitro, JNK is not required for tumor development in vivo. Importantly, the loss of JNK expression resulted in substantial increases in the number and growth of tumor nodules in vivo. Complementation assays demonstrated that this phenotype was caused by JNK deficiency. These data demonstrate that, in contrast to expectations, the normal function of JNK may be to suppress tumor development in vivo. This conclusion is consistent with the presence in human tumors of loss-of-function mutations in the JNK pathway.

Keywords

Footnotes

  • 5 Corresponding author.

  • E-MAIL Roger.Davis{at}Umassmed.Edu; FAX (508) 856-3210.

  • Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1062903.

    • Received November 27, 2002.
    • Accepted January 14, 2003.
| Table of Contents

Life Science Alliance