Activation of Stat3 by v-Src is through a Ras-independent pathway.
V-Src induces tyrosine phosphorylation of various cellular proteins and activates a number of signaling molecules including the Jak family of proteins tyrosine kinases and Stat (signal transducers and activators of transcription) proteins. Many cellular effects elicited by v-Src are mediated through Ras, a molecular switch linking growth factor receptors and non-receptor tyrosine kinases to many downstream effectors. In this report, we demonstrated that v-H-Ras and v-Src both induced cellular transformation. However, the activation of Jak1 and Stat3 were only observed in v-Src transformed cells. Using reporter gene assays, we further showed that activation of Stat3 and possibly of Jak1 by v-Src were mediated through a Ras-independent pathway. As Stat3 activation has recently been shown to be required for cellular transformation by v-Src, our results suggest that activation of the Jak-Stat pathway may serve as a modulator in some but not all transformation processes.
Liu
J J
JJ
Institute of Molecular Medicine, National Taiwan University Medical School, Taipei, Taiwan, ROC.
Nakajima
K
K
Hirano
T
T
Yang-Yen
H F
HF
D016475:3T3 Cells; D000818:Animals; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016391:Genes, src; D051379:Mice; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection; D018631:ras Proteins / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D018631:ras Proteins