Science · 1995 · 943 citations · 20 references
Life SciencesCell BiologyMolecular BiologyCell SignalingOncogenesSignal TransductionOncogene ActivationOncogenic Signaling PathwaysReceptor Tyrosine Kinase OncogenesReceptor Tyrosine Kinase SignalingTranscription Factor OncogenesDna Binding SpecificityElectrophoretic MobilityGrowth FactorsJak-stat Signaling PathwayProtein Tyrosine PhosphorylationSrc Family KinasesStat3 SignalingTyrosine Phosphorylation Signaling
Cytokines and growth factors trigger tyrosine phosphorylation of STAT proteins, directly activating gene expression. The authors examined STAT activation in cells stably transformed by the Src oncogene tyrosine kinase. Electrophoretic mobility, DNA‑binding, and antigenicity assays showed that Src constitutively activates Stat3 (or a related STAT) via tyrosine phosphorylation, correlating with transformation and suggesting Stat3 may contribute to Src‑driven oncogenesis.
Cytokines and growth factors induce tyrosine phosphorylation of signal transducers and activators of transcription (STATs) that directly activate gene expression. Cells stably transformed by the Src oncogene tyrosine kinase were examined for STAT protein activation. Assays of electrophoretic mobility, DNA-binding specificity, and antigenicity indicated that Stat3 or a closely related STAT family member was constitutively activated by the Src oncoprotein. Induction of this DNA-binding activity was accompanied by tyrosine phosphorylation of Stat3 and correlated with Src transformation. These findings demonstrate that Src can activate STAT signaling pathways and raise the possibility that Stat3 contributes to oncogenesis by Src.
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