Interaction of Gα12 with Gα13 and Gαq signaling pathways

JL Gu, S Müller, V Mancino… - Proceedings of the …, 2002 - National Acad Sciences
JL Gu, S Müller, V Mancino, S Offermanns, MI Simon
Proceedings of the National Academy of Sciences, 2002National Acad Sciences
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 α 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 Gα12-deficient mice. In contrast to the Gα13-deficient mice, Gα12-deficient
mice are viable, fertile, and do not show apparent abnormalities. However, Gα12 does not …
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 α 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 Gα12-deficient mice. In contrast to the Gα13-deficient mice, Gα12-deficient mice are viable, fertile, and do not show apparent abnormalities. However, Gα12 does not seem to be entirely redundant, because in the offspring generated from Gα12± Gα13± intercrosses, at least one intact Gα12 allele is required for the survival of animals with only one Gα13 allele. In addition, Gα12 and Gα13 showed a difference in mediating cell migratory response to lysophosphatidic acid in embryonic fibroblast cells. Furthermore, mice lacking both Gα12 and Gαq die in utero at about embryonic day 13. These data indicate that the Gα12-mediated signaling pathway functionally interacts not only with the Gα13- but also with the Gαq/11-mediated signaling systems.
National Acad Sciences