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

Abstract

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