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

The c-Jun NH(2)-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 dem...

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Bibliographic Details
Published in:Genes & development 2003-03, Vol.17 (5), p.629-637
Main Authors: Kennedy, Norman J, Sluss, Hayla K, Jones, Stephen N, Bar-Sagi, Dafna, Flavell, Richard A, Davis, Roger J
Format: Article
Language:English
Subjects:
Animals
Cell Line
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - metabolism
Fibroblasts - metabolism
Fibroblasts - pathology
In Vitro Techniques
JNK Mitogen-Activated Protein Kinases
Male
Mice
Mice, Nude
Mitogen-Activated Protein Kinases - genetics
Mitogen-Activated Protein Kinases - metabolism
Neoplasms, Experimental - genetics
Neoplasms, Experimental - metabolism
Neoplasms, Experimental - pathology
ras Proteins - genetics
ras Proteins - metabolism
Research Paper
Signal Transduction - physiology
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Summary:The c-Jun NH(2)-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.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.1062903