Vitamin K-dependent carboxylation of pulmonary surfactant-associated proteins.
Vitamin K-dependent carboxylation of pulmonary surfactant-associated proteins.
复制标题
肺表面活性剂相关蛋白的维生素 K 依赖性羧化。
DOI：
10.1073/pnas.84.16.5952
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发表时间：
1987
影响因子：
11.1
通讯作者：
Rannels,DE
中科院分区：
文献类型：
--
作者：
Rannels,SR;Gallaher,KJ;Wallin,R;Rannels,DE
大鼠II型肺细胞表达维生素K依赖性羧化酶活性，将14 CO2纳入微粒体蛋白质前体的分子量类似的表面活性剂相关蛋白（SAP）。与存在于肝脏中的羧化前体蛋白相比，这些分子似乎是肺所特有的。针对纯化的大鼠表面活性剂提出的抗体与SAP反应，通过NaDodSO 4/PAGE解析，并与II型肺细胞胞质中含有表面活性剂的板层体。羧化酶催化掺入14 CO2后，微粒体蛋白的NaDodSO 4/PAGE显示与SAP相同的放射性标记的免疫反应性产物。通过SAP水解产物的HPLC分析证实了这些蛋白质中γ-羧基谷氨酸的存在。此外，肺羧化酶活性和SAP在胎肺发育过程中的成熟时间相似。这些结果表明，SAP是羧化的II型细胞通过维生素K依赖性途径类似于肝羧化凝血因子。与凝血系统的进一步类比表明，SAP多肽中的γ-羧基谷氨酸残基在Ca 2+结合中起作用，因此在肺表面活性物质的生理功能中对阳离子和SAP的已知需求中起作用。
Rat type II pneumocytes expressed vitamin K-dependent carboxylase activity that incorporated 14CO2 into microsomal protein precursors of molecular weights similar to those of surfactant-associated proteins (SAP). Compared to carboxylated precursor proteins present in the liver, these molecules appeared to be unique to the lung. Antibodies raised against purified rat surfactant reacted with SAP resolved by NaDodSO4/PAGE and with surfactant-containing lamellar bodies in type II pneumocyte cytoplasm. NaDodSO4/PAGE of microsomal proteins, after carboxylase-catalyzed incorporation of 14CO2, demonstrated radiolabeled, immunoreactive products identical to SAP. The presence of gamma-carboxyglutamic acid in these proteins was confirmed by HPLC analysis of SAP hydrolysates. Furthermore, lung carboxylase activity and SAP matured over similar time courses during fetal lung development. These results show that SAP are carboxylated by type II cells via a vitamin K-dependent pathway analogous to that for hepatic carboxylation of clotting factors. Further analogy to the clotting system suggests that gamma-carboxyglutamic acid residues in SAP polypeptides play a role in Ca2+ binding and thus in the known requirements for both the cation and SAP in the physiological function of pulmonary surfactant.