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首页> 外文期刊>Journal of Cellular Physiology >Plasminogen activator inhibitors regulate cell adhesion through a uPAR-dependent mechanism.
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Plasminogen activator inhibitors regulate cell adhesion through a uPAR-dependent mechanism.

机译：纤溶酶原激活物抑制剂调节细胞通过uPAR-dependent粘附机制。

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Binding of type-1 plasminogen activator inhibitor (PAI-1) to cell surface urokinase (uPA) promotes inactivation and internalization of adhesion receptors (e.g., urokinase receptor (uPAR), integrins) and leads to cell detachment from a variety of extracellular matrices. In this report, we begin to examine the mechanism of this process. We show that neither specific antibodies to uPA, nor active site inhibitors of uPA, can detach the cells. Thus, cell detachment is not simply the result of the binding of macromolecules to uPA and/or of the inactivation of uPA. We further demonstrate that another uPA inhibitor, protease nexin-1 (PN-1), also stimulates cell detachment in a uPA/uPAR-dependent manner. The binding of both inhibitors to uPA leads to the specific inactivation of the matrix-engaged integrins and the subsequent detachment of these integrins from the underlying extracellular matrix (ECM). This inhibitor-mediated inactivation of integrins requires direct interaction between uPAR and those integrins since cells attached to the ECM through integrins incapable of binding uPAR do not respond to the presence of either PAI-1 of PN-1. Although both inhibitors initiate the clearance of uPAR, only PAI-1 triggers the internalization of integrins. However, cell detachment by PAI-1 or PN-1 does not depend on the endocytosis of these integrins since cell detachment was also observed when clearance of these integrins was blocked. Thus, PAI-1 and PN-1 induce cell detachment through two slightly different mechanisms that affect integrin metabolism. These differences may be important for distinct cellular processes that require controlled changes in the subcellular localization of these receptors.
机译：1型纤溶酶原激活物抑制剂的绑定(PAI-1)细胞表面尿激酶(uPA)促进失活和内化的附着力受体(如尿激酶受体(uPAR),整合蛋白)和导致细胞分离各种各样的细胞外基质。报告,我们开始检查的机制的过程。uPA uPA,活性位点抑制剂,可以分离的细胞。简单的绑定的结果大分子uPA和/或失活uPA。抑制剂、蛋白酶nexin-1 (PN-1)刺激细胞分离uPA / uPAR-dependent方式。uPA导致特定的抑制剂失活的matrix-engaged整合蛋白这些整合蛋白的后续分离底层细胞外基质(ECM)。inhibitor-mediated整合蛋白的失活需要uPAR和之间的直接交互这些细胞附着在ECM以来整合蛋白通过整合蛋白无法绑定uPAR做没有回应要么PAI-1的存在PN-1。uPAR结关,只有PAI-1触发整合蛋白的内化。超然PAI-1或PN-1并不取决于这些整合蛋白,因为细胞的内吞作用分离也观察到当间隙这些整合蛋白被阻塞。通过两个稍微诱导细胞分离影响整合素的不同机制新陈代谢。对不同的细胞过程要求控制亚细胞的变化这些受体的定位。

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