Abstract
The heterotrimeric G-protein, Gα12, together with the closely-related Gα13, are members of the G12 class of α-subunits important in mediating the signaling from seven transmembrane domain-spanning receptors. Recent evidence implicating both Gα12 and Gα13 in the activation of signaling pathways involving members of the RHO gene family led us to examine the role of Rac1, RhoA and Cdc42Hs in the transforming properties of Gα12. Asparagine 17 (Asn 17) dominant inhibitory mutants of Rac1, and to a lesser extent RhoA, block focus forming ability of the GTPase-deficient mutant of Gα12 (Gα12 Leu 229) in NIH3T3 cells. In turn, wild-type Gα12 cooperates well with Rac1 Val 12 but not with RhoA Leu 63 mutant in transforming NIH3T3 cells. Interestingly, the morphology of foci induced by Gα12 and RhoA mutants are strikingly similar and is distinct from those displayed by Rac1 Val 12 mutant. The fact that Gα12's ability to induce mitogenesis in NIH3T3 cells is not significantly perturbed by C3 ribosyltransferase suggested that RhoA does not play a major role in Gα12-induced mitogenic events. Activated mutant of Rac1 has previously been demonstrated to stimulate the activity of the stress-induced c-Jun N-terminal kinase/stress-activated protein kinases (JNK/SAPKs). Transient co-transfection of Rac1 Val 12 mutant with the wild-type Gα12 in COS7 cells leads to the further activation of an exogenously expressed hemagglutinin(HA)-tagged JNK. Furthermore, the cooperation between Gα12 and Rac1 in cellular transformation is correlated with their ability to stimulate transcription from c-fos serum response element (SRE).
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Tolkacheva, T., Feuer, B., Lorenzi, M. et al. Cooperative transformation of NIH3T3 cells by Gα12 and Rac1. Oncogene 15, 727–735 (1997). https://doi.org/10.1038/sj.onc.1201229
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DOI: https://doi.org/10.1038/sj.onc.1201229
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