Abstract
Expression of Q205L Galphao (Galphao*), an alpha subunit of heterotrimeric guanine nucleotide-binding proteins (G proteins) that lacks guanosine triphosphatase (GTPase) activity in NIH-3T3 cells, results in transformation. Expression of Galphao* in NIH-3T3 cells activated signal transducer and activator of transcription 3 (Stat3) but not mitogen-activated protein (MAP) kinases 1 or 2. Coexpression of dominant negative Stat3 inhibited Galphao*-induced transformation of NIH-3T3 cells and activation of endogenous Stat3. Furthermore, Galphao* expression increased activity of the tyrosine kinase c-Src, and the Galphao*-induced activation of Stat3 was blocked by expression of Csk (carboxyl-terminal Src kinase), which inactivates c-Src. The results indicate that Stat3 can function as a downstream effector for Galphao* and mediate its biological effects.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Animals
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CSK Tyrosine-Protein Kinase
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Cell Line, Transformed
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Cell Transformation, Neoplastic*
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DNA-Binding Proteins / metabolism*
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Enzyme Activation
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GTP-Binding Protein alpha Subunits
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Genes, Reporter
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Heterotrimeric GTP-Binding Proteins / genetics
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Heterotrimeric GTP-Binding Proteins / metabolism*
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MAP Kinase Signaling System
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Mice
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinases / metabolism
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Neurites / physiology
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Neuronal Plasticity
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Neurons / metabolism
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Neurons / physiology
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Phosphorylation
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Phosphotyrosine / metabolism
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Protein-Tyrosine Kinases / metabolism
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STAT3 Transcription Factor
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Signal Transduction
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Trans-Activators / metabolism*
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Transfection
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src-Family Kinases
Substances
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DNA-Binding Proteins
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GTP-Binding Protein alpha Subunits
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STAT3 Transcription Factor
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Stat3 protein, mouse
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Trans-Activators
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olfactory G protein subunit alpha olf
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Phosphotyrosine
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Protein-Tyrosine Kinases
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CSK Tyrosine-Protein Kinase
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src-Family Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinases
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Heterotrimeric GTP-Binding Proteins