Role of lysyl oxidase propeptide in secretion and enzyme activity.
Role of lysyl oxidase propeptide in secretion and enzyme activity.
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DOI：
10.1002/jcb.22845
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发表时间：
2010-12-01
影响因子：
4
通讯作者：
Kagan, Herbert M.
中科院分区：
文献类型：
--
作者：
Grimsby, Jessica L.;Lucero, Hector A.;Trackman, Philip C.;Ravid, Katya;Kagan, Herbert M.
关键词：
赖氨酰氧化酶（LOX）作为酶原（proLOX）分泌，其在细胞外环境中被蛋白水解加工以释放前肽和成熟的活性LOX。LOX氧化细胞外基质和细胞表面上的许多蛋白质底物的赖氨酰残基，这影响几种生理和疾病状态。虽然LOX前肽（LOX-PP）是糖基化的，但对这种修饰在LOX分泌和活性中的作用知之甚少。为了深入了解这个问题，用天然全长LOX cDNA（前-原-LOX）、N-糖基化无效前-[N/Q]原-LOX cDNA和缺失突变体前-LOX cDNA（称为分泌型LOX）转染细胞，其中成熟LOX靶向分泌途径而没有其N-末端前肽序列。结果表明，LOX-PP的糖基化对于pro-LOX的分泌和细胞外加工不是必需的，但对于所得成熟LOX的最佳酶活性是必需的。前肽序列的完全缺失阻止成熟LOX离开内质网（ER）。综上所述，我们的研究指出了LOX-PP对pro-LOX从ER退出的要求，并且首次强调了LOX-PP糖基化对LOX酶活性的影响。
Lysyl oxidase (LOX) is secreted as a proenzyme (proLOX) that is proteolytically processed in the extracellular milieu to release the propeptide and mature, active LOX. LOX oxidizes lysyl residues of a number of protein substrates in the extracellular matrix and on the cell surface, which impacts several physiological and disease states. Although the LOX propeptide (LOX-PP) is glycosylated, little is known about the role of this modification in LOX secretion and activity. To gain insight into this issue, cells were transfected with native, full-length LOX cDNA (pre-pro-LOX), the N-glycosylation null pre-[N/Q]pro-LOX cDNA and the deletion mutant pre-LOX cDNA, referred to as secretory LOX, in which mature LOX is targeted to the secretory pathway without its N-terminal propeptide sequence. The results show that glycosylation of the LOX-PP is not required for secretion and extracellular processing of pro-LOX but it is required for optimal enzyme activity of the resulting mature LOX. Complete deletion of the propeptide sequence prevents mature LOX from exiting the endoplasmic reticulum (ER). Taken together, our study points out the requirement of the LOX-PP for pro-LOX exit from the ER and is the first to highlight the influence of LOX-PP glycosylation on LOX enzyme activity.
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影响因子：
2.9
作者：
CRONLUND, AL;SMITH, BD;KAGAN, HM
通讯作者：
KAGAN, HM
影响因子：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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