Interaction of Gα(12) with Gα(13) and Gα(q) signaling pathways

The G(12) subfamily of heterotrimeric G-proteins consists of two members, G(12) and G(13). Gene-targeting studies have revealed a role for G(13) in blood vessel development. Mice lacking the α subunit of G(13) die around embryonic day 10 as the result of an angiogenic defect. On the other hand, the physiological role of G(12) is still unclear. To address this issue, we generated Gα(12)-deficient mice. In contrast to the Gα(13)-deficient mice, Gα(12)-deficient mice are viable, fertile, and do not show apparent abnormalities. However, Gα(12) does not seem to be entirely redundant, because in the offspring generated from Gα(12)± Gα(13)± intercrosses, at least one intact Gα(12) allele is required for the survival of animals with only one Gα(13) allele. In addition, Gα(12) and Gα(13) showed a difference in mediating cell migratory response to lysophosphatidic acid in embryonic fibroblast cells. Furthermore, mice lacking both Gα(12) and Gα(q) die in utero at about embryonic day 13. These data indicate that the Gα(12)-mediated signaling pathway functionally interacts not only with the Gα(13)- but also with the Gα(q/11)-mediated signaling systems.