c-Src activates both STAT1 and STAT3 in PDGF-stimulated NIH3T3 cells.
Treatment of cells with PDGF and EGF specifically induces STAT1 and STAT3, which became phosphorylated on tyrosine residues to form homo and heterodimers: in these configurations they translocate into the nucleus where they act as transcription activators. However little is known about the activation of STATs in growth factor receptor signal transduction. Recently it has been shown that v-Src modulates the tyrosine phosphorylation of STAT3 but not of STAT1. Here we report that the cellular Src tyrosine kinase is involved in the activation of both STAT1 and STAT3 in PDGF stimulated NIH3T3 cells. Both tyrosine phosphorylation and DNA binding activity of STAT1 and STAT3 are up-regulated in c-Src overexpressing cells, while we observe the opposite phenomenon in cells overexpressing the dominant negative Src. Furthermore, our results show that STAT1 co-immunoprecipitates with c-Src, suggesting that the activation of STATs by Src occurs via a direct interaction. Taken together, these data suggest that c-Src is involved in activation of both STAT1 and 3 in PDGF signal transduction.
Cirri
P
P
Dipartimento di Scienze Biochimiche, Instituto di Medicina Interna, Università di Firenze, Italy.
Chiarugi
P
P
Marra
F
F
Raugei
G
G
Camici
G
G
Manao
G
G
Ramponi
G
G
D016475:3T3 Cells; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D011485:Protein Binding / Q000235:genetics; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; D010982:Platelet-Derived Growth Factor; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D014443:Tyrosine; D016392:Proto-Oncogene Proteins pp60(c-src)