Interaction of Gα ₁₂ with Gα ₁₃ and Gα _q signaling pathways

Abstract

The G12 subfamily of heterotrimeric G-proteins consists of two members, G 12 and G13. Gene-targeting studies have revealed a role for G 13 in blood vessel development. Mice lacking the ␣ subunit of G 13 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␣ 13-but also with the G␣q/11-mediated signaling systems.

Identification and molecular characterization of the Gα12–Rho guanine nucleotide exchange factor pathway in Caenorhabditis elegans

“…Embryos carrying one G␣12 allele with G␣13 null survived until E9, whereas those that had one G␣12 and one G␣13 alleles were viable. These genetic studies revealed that both an overlapping and a distinct function of G␣12-and G␣13-mediated signaling exists in mouse embryonic development (8,29). The G␣12-RhoGEF-Rho pathway in C. elegans is also critical in embryonic development.…”

G13 is an essential mediator of platelet activation in hemostasis and thrombosis

“…Mice lacking Gα 13 , the α-subunit of G 13 , die in utero because of a defect in angiogenesis, whereas Gα 12 -deficient mice are phenotypically normal 10,11 . To circumvent embryonic lethality of mice deficient in Gα 13 and to study the role of Gα 12 -and Gα 13 -mediated signaling in platelet activation, we used Cre/loxP-mediated recombination to conditionally inactivate Gna13, the gene encoding Gα 13 , alone or in a Gα 12 -deficient (Gna12 -/-) background.…”

G Proteins G12 and G13 Control the Dynamic Turnover of Growth Factor-induced Dorsal Ruffles

“…In G␣ 12 G␣ 13 knock-out MEF cells, neither G protein-coupled receptors for thrombin or lysophosphatidic acid nor receptor tyrosine kinases for PDGF or epidermal growth factor induced migration of these cells (18,19,23). To visualize directly the effect of G␣ 12 and G␣ 13 on actin cytoskeletal reorganization, we utilized live cell imaging techniques to compare the dynamics of actin cytoskeletal reorganization in wild-type and G␣ 12 G␣ 13 knock-out MEF cells.…”

“…Cell Culture and Transfection-G␣ 12 Ϫ/Ϫ G␣ 13 Ϫ/Ϫ MEF cells were provided by J. Gu and M. Simon (California Institute of Technology) and have been previously described (18,19). Cells were grown in DMEM containing 10% fetal bovine serum and penicillin/streptomycin.…”

“…The PCR products of chicken Src constitutively active mutant SrcE378G and SrcY527F cDNAs were subcloned into pcDNA3.1/hyg/myc. HA-Rac1G12V and HA-Rac1T14N were obtained from Guthrie Research Institute.Cell Culture and Transfection-G␣ 12 Ϫ/Ϫ G␣ 13 Ϫ/Ϫ MEF cells were provided by J. Gu and M. Simon (California Institute of Technology) and have been previously described (18,19). Cells were grown in DMEM containing 10% fetal bovine serum and penicillin/streptomycin.…”