ADAM Proteases and Gastrointestinal Function.
ADAM Proteases and Gastrointestinal Function.
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ADAM 蛋白酶和胃肠功能。
DOI：
10.1146/annurev-physiol-021014-071720
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发表时间：
2016
影响因子：
18.2
通讯作者：
Dempsey PJ
中科院分区：
文献类型：
--
作者：
Jones JC;Rustagi S;Dempsey PJ
去整合素和金属蛋白酶（亚当斯）是调节多种细胞功能的细胞表面蛋白酶家族，包括细胞粘附、迁移、细胞信号传导和蛋白水解。具有蛋白水解活性的亚当斯负责膜相关蛋白的胞外域脱落。亚当斯响应细胞外环境的变化（例如，炎症），并在协调局部微环境内的细胞间通讯中发挥核心作用。ADAM 10和ADAM 17是在胃肠道中研究最多的ADAM家族成员。亚当斯调节许多与肠道发育、细胞命运特化和肠道干细胞/祖细胞群维持相关的细胞过程。几种通过亚当斯进行胞外域脱落的信号传导途径分子[例如，表皮生长因子受体（EGFR）/ErbB和肿瘤坏死因子α（TNFα）受体（TNFR）家族的配体和受体]有助于驱动和控制肠道炎症和损伤/修复反应。通过异常的ADAM表达或持续的ADAM活性的这些过程的失调与慢性炎症、炎症相关的癌症和肿瘤发生有关。
A disintegrin and metalloproteinases (ADAMs) are a family of cell surface proteases that regulate diverse cellular functions, including cell adhesion, migration, cellular signaling, and proteolysis. Proteolytically active ADAMs are responsible for ectodomain shedding of membrane-associated proteins. ADAMs rapidly modulate key cell signaling pathways in response to changes in the extracellular environment (e.g., inflammation) and play a central role in coordinating intercellular communication within the local microenvironment. ADAM10 and ADAM17 are the most studied members of the ADAM family in the gastrointestinal tract. ADAMs regulate many cellular processes associated with intestinal development, cell fate specification, and the maintenance of intestinal stem cell/progenitor populations. Several signaling pathway molecules that undergo ectodomain shedding by ADAMs [e.g., ligands and receptors from epidermal growth factor receptor (EGFR)/ErbB and tumor necrosis factor α (TNFα) receptor (TNFR) families] help drive and control intestinal inflammation and injury/repair responses. Dysregulation of these processes through aberrant ADAM expression or sustained ADAM activity is linked to chronic inflammation, inflammation-associated cancer, and tumorigenesis.