Vitamin K-dependent proteins in Ciona intestinalis, a basal chordate lacking a blood coagulation cascade
Vitamin K-dependent proteins in Ciona intestinalis, a basal chordate lacking a blood coagulation cascade
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DOI：
10.1073/pnas.0607543103
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发表时间：
2006-10-24
影响因子：
11.1
通讯作者：
Davie, Earl W.
中科院分区：
文献类型：
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作者：
Kulman, John D.;Harris, Jeff E.;Davie, Earl W.
我们已经分离和测序了几个cDNA来自海鞘Ciona Ciona，编码维生素K依赖蛋白。其中四个编码含有γ-羧基谷氨酸（Gla）结构域的蛋白质，我们将其命名为Ci-Gla 1至Ci-Gla 4。另外两个cDNA编码γ-谷氨酰羧化酶和维生素K环氧化物还原酶的表观直系同源物。Ci-Gla 1在CHO细胞中表达时发生γ-谷氨酰羧化，与Gla-RTK同源，Gla-RTK是一种先前在相关海鞘中鉴定的推定受体酪氨酸激酶。其余三种Gla结构域蛋白类似于参与基本发育过程、补体调节和血液凝固的蛋白。这些蛋白质在整个发育过程中通常以低水平表达，并且表现出相对恒定的表达（Ci-Gla 1、γ-谷氨酰羧化酶和维生素K环氧化物还原酶）或时空调节（Ci-Gla 2、-3和-4）。这些结果表明，维生素K依赖性Gla结构域的进化出现之前，脊椎动物和尿索动物的分歧，并建议新的功能Gla结构域蛋白质不同的脊椎动物止血的作用。此外，这些发现强调了C。维生素K依赖的生理现象，这可能是保守的脊索动物亚门之间的研究模式生物。
We have isolated and sequenced several cDNAs derived from the sea squirt Ciona intestinalis that encode vitamin K-dependent proteins. Four of these encode gamma-carboxyglutamic acid (Gla) domain-containing proteins, which we have named Ci-Gla1 through Ci-Gla4. Two additional cDNAs encode the apparent orthologs of gamma-glutamyl carboxylase and vitamin K epoxide reductase. Ci-Gla1 undergoes gamma-glutamyl carboxylation when expressed in CHO cells and is homologous to Gla-RTK, a putative receptor tyrosine kinase previously identified in a related ascidian. The remaining three Gla domain proteins are similar to proteins that participate in fundamental developmental processes, complement regulation, and blood coagulation. These proteins are generally expressed at low levels throughout development and exhibit either relatively constant expression (Ci-Gla1, gamma-glutamyl carboxylase, and vitamin K epoxide reductase) or spatiotemporal regulation (Ci-Gla2, -3, and -4). These results demonstrate the evolutionary emergence of the vitamin K-dependent Gla domain before the divergence of vertebrates and urochordates and suggest novel functions for Gla domain proteins distinct from their roles in vertebrate hemostasis. In addition, these findings highlight the usefulness of C. intestinalis as a model organism for investigating vitamin K-dependent physiological phenomena, which may be conserved among the chordate subphyla.