Ra Hyun-Jeong, Parks William C
Center for Lung Biology, University of Washington, Seattle, WA 98109, USA.
Matrix Biol. 2007 Oct;26(8):587-96. doi: 10.1016/j.matbio.2007.07.001. Epub 2007 Jul 7.
As their name implies, MMPs were first described as proteases that degrade extracellular matrix proteins, such as collagens, elastin, proteoglycans, and laminins. However, studies of MMP function in vivo have revealed that these proteinases act on a variety of extracellular protein substrates, often to activate latent forms of effector proteins, such as antimicrobial peptides and cytokines, or to alter protein function, such as shedding of cell-surface proteins. Because their substrates are diverse, MMPs are involved in variety of homeostatic functions, such as bone remodeling, wound healing, and several aspects of immunity. However, MMPs are also involved in a number of pathological processes, such as tumor progression, fibrosis, chronic inflammation, tissue destruction, and more. A key step in regulating MMP proteolysis is the conversion of the zymogen into an active proteinase. Several proMMPs are activated in the secretion pathway by furin proprotein convertases, but for most the activation mechanisms are largely not known. In this review, we discuss both authentic and potential mechanisms of proMMP activation.
顾名思义，基质金属蛋白酶最初被描述为可降解细胞外基质蛋白的蛋白酶，如胶原蛋白、弹性蛋白、蛋白聚糖和层粘连蛋白。然而，对基质金属蛋白酶体内功能的研究表明，这些蛋白酶作用于多种细胞外蛋白质底物，通常是激活效应蛋白的潜在形式，如抗菌肽和细胞因子，或改变蛋白质功能，如细胞表面蛋白的脱落。由于其底物多种多样，基质金属蛋白酶参与多种稳态功能，如骨重塑、伤口愈合和免疫的多个方面。然而，基质金属蛋白酶也参与许多病理过程，如肿瘤进展、纤维化、慢性炎症、组织破坏等。调节基质金属蛋白酶蛋白水解的关键步骤是将酶原转化为活性蛋白酶。几种前基质金属蛋白酶在分泌途径中被弗林蛋白酶原转化酶激活，但对于大多数来说，激活机制在很大程度上尚不清楚。在这篇综述中，我们讨论了前基质金属蛋白酶激活的真实机制和潜在机制。
