Lysyl Oxidase Binds Transforming Growth Factor-β and Regulates Its Signaling via Amine Oxidase Activity
Lysyl Oxidase Binds Transforming Growth Factor-β and Regulates Its Signaling via Amine Oxidase Activity
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DOI：
10.1074/jbc.m803142200
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发表时间：
2008-12-05
影响因子：
4.8
通讯作者：
Yamauchi, Mitsuo
中科院分区：
文献类型：
--
作者：
Atsawasuwan, Phimon;Mochida, Yoshiyuki;Yamauchi, Mitsuo
赖氨酰氧化酶（LOX）是一种对胶原和弹性蛋白交联起始起关键作用的胺氧化酶，最近被证明可能通过调节生长因子的功能来调节细胞活性。在这项研究中，我们研究了LOX和转化生长因子-β 1（TGF-β 1）之间的相互作用，骨中丰富的一种有效的生长因子，LOX对TGF-β 1信号传导的影响，及其潜在的机制。成熟LOX和成熟TGF-β 1之间的特异性结合通过免疫沉淀和谷胱甘肽S-转移酶下拉试验在体外被证明。这两种蛋白质共定位在成骨细胞培养系统中的细胞外基质中，并且在骨基质的矿物质相关部分中鉴定了结合复合物。此外，LOX可能通过其胺氧化酶活性抑制TGF-β 1诱导的Smad 3磷酸化。这些数据表明，LOX结合成熟的TGF-β 1，并酶促调节其在骨中的信号传导，因此可能在骨的维持和重塑中发挥重要作用。
Lysyl oxidase (LOX), an amine oxidase critical for the initiation of collagen and elastin cross-linking, has recently been shown to regulate cellular activities possibly by modulating the functions of growth factors. In this study, we investigated the interaction between LOX and transforming growth factor-beta 1 (TGF-beta 1), a potent growth factor abundant in bone, the effect of LOX on TGF-beta 1 signaling, and its potential mechanism. The specific binding between mature LOX and mature TGF-beta 1 was demonstrated by immunoprecipitation and glutathione S-transferase pulldown assay in vitro. Both proteins were colocalized in the extracellular matrix in an osteoblastic cell culture system, and the binding complex was identified in the mineral-associated fraction of bone matrix. Furthermore, LOX suppressed TGF-beta 1-induced Smad3 phosphorylation likely through its amine oxidase activity. The data indicate that LOX binds to mature TGF-beta 1 and enzymatically regulates its signaling in bone and thus may play an important role in bone maintenance and remodeling.