Interaction of G[[alpha].sub.12] with G[[alpha].sub.13] and G[[alpha].sub.q] signaling pathways

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