Romero E E, Velazquez-Estades L J, Deo R, Schapiro B, Roth D A
Division of Hematology-Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Exp Cell Res. 1998 Sep 15;243(2):334-46. doi: 10.1006/excr.1998.4151.
Vitamin K-dependent carboxylase catalyzes the posttranslational modification of glutamate to gamma-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 by in situ hybridization. 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.
维生素K依赖性羧化酶催化其底物维生素K依赖性蛋白（VKDPs）中谷氨酸的翻译后修饰，生成γ-羧基谷氨酸（Gla）。这种修饰是VKDPs发挥活性所必需的。最近的证据表明，VKDPs具有以前未被认识到的作用，即作为在细胞生长、黏附和凋亡调节中起重要作用的信号分子，这表明VKDPs以及羧化酶具有发育功能。羧化酶在发育过程中的组织分布和功能尚不清楚。在本研究中，我们分离并鉴定了编码大鼠羧化酶的全长cDNA，并通过原位杂交在细胞水平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。肝细胞是血液凝固中VKDPs的主要合成部位，在妊娠后期表达羧化酶mRNA，而中枢神经系统、间充质和骨骼组织在大鼠胚胎发育早期就表达羧化酶mRNA。胚胎发育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的形成受到发育调控。这些研究表明，维生素K依赖性羧化是胚胎VKDP功能的重要调节因子。
