Interaction of G alpha(12) with G alpha(13) and G alpha(q) signaling pathways.
Interaction of G alpha(12) with G alpha(13) and G alpha(q) signaling pathways.
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发表时间：
2002
影响因子：
11.1
通讯作者：
Jennifer L Gu;Stefan Müller;V. Mancino;Stefan Offermanns;Melvin I. Simon
中科院分区：
文献类型：
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作者：
Jennifer L Gu;Stefan Müller;V. Mancino;Stefan Offermanns;Melvin I. Simon
异源三聚体 G 蛋白的 G(12) 亚家族由两个成员组成：G(12) 和 G(13)。基因靶向研究揭示了 G(13) 在血管发育中的作用。缺乏 G(13) α 亚基的小鼠在胚胎第 10 天左右就会因血管生成缺陷而死亡。另一方面，G(12)的生理作用仍不清楚。为了解决这个问题，我们培育了 G alpha(12) 缺陷小鼠。与 G α(13) 缺陷小鼠相比，G α(12) 缺陷小鼠能够存活、具有生育能力，并且没有表现出明显的异常。然而，G alpha(12)似乎并不完全多余，因为在G alpha(12)+/- G alpha(13)+/-杂交产生的后代中，只有一个G alpha(13)等位基因的动物的生存需要至少一个完整的G alpha(12)等位基因。此外，G α(12) 和G α(13) 在介导胚胎成纤维细胞中对溶血磷脂酸的细胞迁移反应方面表现出差异。此外，同时缺乏 G α(12) 和 G α(q) 的小鼠在胚胎第 13 天左右就会在子宫内死亡。这些数据表明，G α(12) 介导的信号传导途径不仅与 G α(13) 介导的信号传导系统功能性相互作用，而且还与 G α(q/11) 介导的信号传导系统相互作用。
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.