Interaction of Gα₁₂ with Gα₁₃ 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 a 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 Galpha(12)-deficient mice. In contrast to the Galpha(13)-deficient mice, Galpha(12)-deficient mice are viable, fertile, and do not show apparent abnormalities. However, Galpha(12) does not seem to be entirely redundant, because in the offspring generated from Galpha(12)+/-Galpha(13) intercrosses, at least one intact Galpha(12) allele is required for the survival of animals with only one Galpha(13) allele. In addition, Galpha(12) and Galpha(13) showed a difference in mediating cell migratory response to lysophosphatidic acid in embryonic fibroblast cells. Furthermore, mice lacking both Galpha(12) and Galpha(q) die in utero at about embryonic day 13. These data indicate that the Galpha(12)-mediated signaling pathway functionally interacts not only with the Galpha(13)- but also with the Galpha(q/11)-mediated signaling systems.