Stat3-Mediated Transformation of NIH-3T3 Cells by the Constitutively Active Q205L Gαo Protein

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Science  07 Jan 2000:
Vol. 287, Issue 5450, pp. 142-144
DOI: 10.1126/science.287.5450.142

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Expression of Q205L Gαo(Gαo*), 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 Gαo* 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 Gαo*-induced transformation of NIH-3T3 cells and activation of endogenous Stat3. Furthermore, Gαo* expression increased activity of the tyrosine kinase c-Src, and the Gαo*-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 Gαo* and mediate its biological effects.

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