Interaction of G alpha(12) with G alpha(13) and G alpha(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 alpha 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 G alpha(12)-deficient mice. In contrast to the G alpha(13)-deficient mice, G alpha(12)-deficient mice are viable, fertile, and do not show apparent abnormalities. However, G alpha(12) does not seem to be entirely redundant, because in the offspring generated from G alpha(12)+/- G alpha(13)+/- intercrosses, at least one intact G alpha(12) allele is required for the survival of animals with only one G alpha(13) allele. In addition, G alpha(12) and G alpha(13) showed a difference in mediating cell migratory response to lysophosphatidic acid in embryonic fibroblast cells. Furthermore, mice lacking both G alpha(12) and G alpha(q) die in utero at about embryonic day 13. These data indicate that the G alpha(12)-mediated signaling pathway functionally interacts not only with the G alpha(13)- but also with the G alpha(q/11)-mediated signaling systems.
Gu
Jennifer L
JL
Division of Biology, 147-75 California Institute of Technology, Pasadena, CA 91125, USA.
Müller
Stefan
S
Mancino
Valeria
V
Offermanns
Stefan
S
Simon
Melvin I
MI
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology; D005260:Female; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D020962:Heterotrimeric GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000502:physiology*
D004268:DNA-Binding Proteins; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins