Interaction of G 12 with G 13 and G q signaling pathways

The G12 subfamily of heterotrimeric G-proteins consists of two members, G12 and G13. Gene-targeting studies have revealed a role for G13 in blood vessel development. Mice lacking the subunit of G13 die around embryonic day 10 as the result of an angiogenic defect. On the other hand, the physiological role of G12 is still unclear. To address this issue, we generated G 12-deficient mice. In contrast to the G 13-deficient mice, G 12-deficient mice are viable, fertile, and do not show apparent abnormalities. However, G 12 does not seem to be entirely redundant, because in the offspring generated from G 12 G 13 intercrosses, at least one intact G 12 allele is required for the survival of animals with only one G 13 allele. In addition, G 12 and G 13 showed a difference in mediating cell migratory response to lysophosphatidic acid in embryonic fibroblast cells. Furthermore, mice lacking both G 12 and G q die in utero at about embryonic day 13. These data indicate that the G 12-mediated signaling pathway functionally interacts not only with the G 13but also with the G q/11-mediated signaling systems.