PAI-1: An Integrator of Cell Signaling and Migration.
PAI-1: An Integrator of Cell Signaling and Migration.
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DOI：
10.1155/2011/562481
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发表时间：
2011
影响因子：
--
通讯作者：
Higgins PJ
中科院分区：
文献类型：
--
作者：
Czekay RP;Wilkins-Port CE;Higgins SP;Freytag J;Overstreet JM;Klein RM;Higgins CE;Samarakoon R;Higgins PJ
细胞迁移，通过简单的表面或通过复杂的基质屏障，需要协调分离/再粘附周期，涉及细胞外基质的结构成分和它们的表面结合元件（整合素），和细胞周围蛋白水解微环境的精确调节。现在很明显，几种蛋白酶和蛋白酶抑制剂，最值得注意的是尿激酶纤溶酶原激活物（uPA）和纤溶酶原激活物抑制剂1型（派-1），也与几种细胞表面受体相互作用，转导细胞内信号，显著影响运动和增殖程序。这些事件似乎与uPA/派-1作为基于纤溶酶的蛋白水解级联的调节剂的原始功能不同。派-1与特定基质组分（即，玻连蛋白）、低密度脂蛋白受体相关蛋白-1（LRP 1）和uPA/uPA受体复合物对迁移表型具有显著的影响，并且可能是派-1缺乏和过表达的病理生理学后果的基础。本文着重于派-1作为细胞迁移表型的主要机制决定因素的日益复杂的作用。
Cellular migration, over simple surfaces or through complex stromal barriers, requires coordination between detachment/re-adhesion cycles, involving structural components of the extracellular matrix and their surface-binding elements (integrins), and the precise regulation of the pericellular proteolytic microenvironment. It is now apparent that several proteases and protease inhibitors, most notably urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1), also interact with several cell surface receptors transducing intracellular signals that significantly affect both motile and proliferative programs. These events appear distinct from the original function of uPA/PAI-1 as modulators of the plasmin-based proteolytic cascade. The multifaceted interactions of PAI-1 with specific matrix components (i.e., vitronectin), the low-density lipoprotein receptor-related protein-1 (LRP1), and the uPA/uPA receptor complex have dramatic consequences on the migratory phenotype and may underlie the pathophysiologic sequalae of PAI-1 deficiency and overexpression. This paper focuses on the increasingly intricate role of PAI-1 as a major mechanistic determinant of the cellular migratory phenotype.