Activation of STAT3 by specific Gα subunits and multiple Gβγ dimers

The hematopoietic-specific Gq subfamily members, Gα16 and Gα14 proteins have recently been shown to be capable of stimulating the signal transducer and activator of transcription 3 (STAT3) as well as STAT1. In the present study we examined whether this activation was STAT-member specific as well as determining the possible involvement of Gβγ dimers. Despite clear stimulation of STAT3, the constitutively active mutants of Gα16 (Gα16QL) and Gα14 (Gα14QL) failed to induce the phosphorylation of several STAT family members, including STAT2, STAT4 and STAT5 in human embryonic kidney 293 cells. On the other hand, transient expression of specific combinations of Gβγ complexes induced STAT3 phosphorylation. Among the 48 combinations tested, 13 permutations of Gβγ stimulated STAT3 phosphorylation and all of them contain the neuronal-specific Gγ2, Gγ4, Gγ7 and Gγ9. These results suggested that the activation of STAT family members by Gα16 or Gα14 was selective and that distinct combinations of Gβγ complexes can also regulate the STAT signaling pathway.