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首页> 外文期刊>Frontiers in bioscience: a journal and virtual library >MT-SP1 proteolysis and regulation of cell-microenvironment interactions.
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MT-SP1 proteolysis and regulation of cell-microenvironment interactions.

机译：MT-SP1蛋白水解和细胞微环境相互作用的调控。

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摘要

MT-SP1 is a type II transmembrane serine protease implicated in a range of human cancers including those of the breast, cervix, ovaries, prostate, colon and gastrointestinal tract. Mouse models have shown it to be critical for proper epidermal development and postnatal survival. However, the role of this enzyme in normal and malignant biology has not yet been fully elucidated. Several groups have identified putative substrates of MT-SP1 in an effort to understand the possible biological processes in which this protease may be involved. Methods for substrate identification include comparing known protein cleavage sequences with MT-SP1 specificity data, in vitro cleavage assays, examining genetic microarrays for enzyme/substrate coexpression, immunohistochemistry for colocalization, and a variety of phenotypic observations using cell culture and mouse models. Given the inherent limitations of each individual method, substrate plausibility is best substantiated using a combination of experimental approaches. Here we review MT-SP1 substrates identified to date and the possible physiological implications of substrate cleavage in cell-microenvironment interactions. This data indicates that MT-SP1 is capable of playing roles in growth factor activation, receptor activation and inactivation, protease activation, and ectodomain shedding. We also present for the first time vascular endothelial growth factor receptor 2 (VEGFR-2) as a putative substrate for MT-SP1.
机译：MT-SP1是一种II型跨膜丝氨酸蛋白酶，涉及多种人类癌症，包括乳腺癌，宫颈癌，卵巢癌，前列腺癌，结肠癌和胃肠道癌。小鼠模型显示它对于适当的表皮发育和产后存活至关重要。但是，该酶在正常和恶性生物学中的作用尚未完全阐明。几个小组已经确定了MT-SP1的假定底物，以了解该蛋白酶可能参与的可能的生物学过程。底物鉴定的方法包括将已知的蛋白质裂解序列与MT-SP1特异性数据进行比较，体外裂解测定，检查酶/底物共表达的基因芯片，共定位的免疫组织化学以及使用细胞培养和小鼠模型进行的各种表型观察。考虑到每种方法的固有局限性，结合实验方法可以最好地证明底物的真实性。在这里，我们回顾了迄今为止确定的MT-SP1底物以及在细胞-微环境相互作用中底物裂解的可能的生理意义。该数据表明MT-SP1能够在生长因子激活，受体激活和失活，蛋白酶激活和胞外域脱落中起作用。我们还首次提出了血管内皮生长因子受体2（VEGFR-2）作为MT-SP1的假定底物。

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