Cloning of rat vitamin K-dependent gamma-glutamyl carboxylase and developmentally regulated gene expression in postimplantation embryos.

Cloning of rat vitamin K-dependent gamma-glutamyl carboxylase and developmentally regulated gene expression in postimplantation embryos.
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大鼠维生素 K 依赖性 γ-谷氨酰羧化酶的克隆和植入后胚胎中发育调控的基因表达。

DOI:
10.1006/excr.1998.4151
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发表时间:
1998
期刊:
Experimental cell research.
影响因子:
--
通讯作者:
Roth,DA
Roth,DA
中科院分区:
--
文献类型:
--
作者:
Romero,EE;Velazquez-Estades,LJ;Deo,R;Schapiro,B;Roth,DA

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维生素 K 依赖性羧化酶催化其底物维生素 K 依赖性蛋白 (VKDP) 中的谷氨酸翻译后修饰为 γ-羧基谷氨酸 (Gla)。 VKDP 的活动需要进行此修改。最近的证据表明,VKDP 作为信号分子在细胞生长、粘附和凋亡调节中发挥着重要作用,这一作用此前未被认识,这表明 VKDP 以及羧化酶的发育功能。发育过程中羧化酶的组织分布和功能尚不清楚。在这项研究中,我们分离并表征了编码大鼠羧化酶的全长cDNA,并通过原位杂交在细胞水平上分析了该基因在大鼠胚胎中的表达。我们证明该基因的表达以发育和组织特异性方式受到高度调控。肝细胞是凝血 VKDP 合成的主要部位,在妊娠晚期表达羧化酶 mRNA,而中枢神经系统、间充质和骨骼组织则在大鼠胚胎发生早期表达羧化酶 mRNA。胚胎发生过程中羧化酶基因的组织特异性时间表达表明维生素 K 依赖性羧化和 Gla 的形成受到发育调节。这些研究表明维生素 K 依赖性羧化是胚胎 VKDP 功能的重要调节剂。
Vitamin K-dependent carboxylase catalyzes the posttranslational modification of glutamate to γ-carboxyglutamate (Gla) in its substrates, the vitamin K-dependent proteins (VKDPs). This modification is required for the activities of the VKDPs. Recent evidence demonstrates previously unrecognized roles for VKDPs as signaling molecules important in the regulation of cell growth, adhesion, and apoptosis, suggesting developmental functions for VKDPs and hence the carboxylase. The tissue distribution and functions of carboxylase in development are unknown. In this study, we isolated and characterized the full-length cDNA encoding the rat carboxylase and analyzed, at the cellular level, the expression of this gene in rat embryos byin situhybridization. We demonstrate that the expression of this gene is highly regulated in a developmental and tissue-specific manner. Hepatocytes, the major site of synthesis of VKDPs of blood coagulation, express carboxylase mRNA late in gestation, in contrast to the central nervous system, mesenchymal, and skeletal tissues which express carboxylase mRNA early during rat embryogenesis. The tissue-specific temporal expression of the carboxylase gene during embryogenesis indicates that vitamin K-dependent carboxylation and the formation of Gla is developmentally regulated. These studies suggest that vitamin K-dependent carboxylation is an important modulator of embryonic VKDP function.
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