Modulation of the Binding of Matrix Gla Protein (MGP) to Bone Morphogenetic Protein-2 (BMP-2)
Modulation of the Binding of Matrix Gla Protein (MGP) to Bone Morphogenetic Protein-2 (BMP-2)
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DOI：
10.1055/s-0037-1614168
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发表时间：
2000-12
影响因子：
6.7
通讯作者：
R. Wallin;D. Cain;S. Hutson;D. Sane;R. Loeser
中科院分区：
文献类型：
--
作者：
R. Wallin;D. Cain;S. Hutson;D. Sane;R. Loeser
基质Gla蛋白（MGP）是动脉壁钙化的抑制剂，但抑制机制尚未解决。由于软骨形成已被确定在钙化动脉MPG无效小鼠，我们假设，本地生产的MGP可能会抑制钙化，通过中和骨形态发生蛋白（BMP）作为促进软骨形成和骨形成的已知效果。作为检验这一假设的第一步，我们证明了MGP是125 I-BMP-2的结合蛋白。最佳结合依赖于金属，这表明MGP中的金属结合Gla区参与。尽管γ-羧化酶结合位点是成熟蛋白质序列的一部分，但MGP显示经历Ca++诱导的构象变化。这些数据表明MGP在分泌途径中比其他维生素K依赖性蛋白更早成熟。使用抗体试图鉴定牛血清中的MGP。构象特异性MGP抗体也显示出识别凝血酶原和因子X中的Gla区域，但不能识别血清中的MGP。这一发现得到电泳数据的支持，电泳数据表明，柠檬酸钡吸收的维生素K依赖性血清蛋白中不存在MGP。我们的结论是，MGP不存在于正常牛血清中。
Summary Matrix Gla protein (MGP) is an inhibitor of calcification of the arterial wall but the mechanism of inhibition has not been resolved. Since chondrogenesis has been identified in calcified arteries from MPG null mice, we hypothesized that locally produced MGP might inhibit calcification by neutralizing the known effect of bone morphogenetic proteins (BMPs) as promotors of chondrogenesis and bone formation. As the first step to test this hypothesis, we demonstrate that MGP is a binding protein for 125I-BMP-2. Optimal binding is dependent on metals which suggests that the metal binding Gla region in MGP is involved. MGP is shown to undergo a Ca++ induced conformational change despite the presence of the γ-carboxylase binding site being part of the mature protein sequence. The data propose that MGP matures earlier in the secretory pathway than other vitamin K-dependent proteins. Antibodies were used in an attempt to identify MGP in bovine serum. Conformational specific MGP antibodies were shown to also recognize the Gla region in prothrombin and factor X but did not identify MGP in serum. This finding is supported by electrophoresis data which demonstrate the absence of MGP among Ba-citrate absorbed vitamin K-dependent serum proteins. We conclude that MGP does not exist in normal bovine serum.