Heterotrimeric guanine nucleotide-binding proteins (G proteins) couple activation of G protein-coupled receptors on the cell surface to modulation of a large array of diverse biological effects. The subunits of the G proteins interact with effectors to bring about such responses. A member of the Gα subunit family, Gαo, when mutated to remain constantly in an active form (Gαo*), causes transformation of NIH 3T3 cells. Ram et al. explored the signaling pathways that mediate this effect of Gαo. They find that Stat3 (for signal transducer and activator of transcription 3) is activated in cells expressing Gαo* and appears to be necessary for the growth-promoting action of Gαo*. Stats are transcription factors activated by tyrosine phosphorylation in response to cytokine receptors (which are not coupled to G proteins). In this case, however, Gαo seems to stimulate the tyrosine kinase c-Src, which in turn activates Stat3 and contributes to abnormal cellular proliferation.