Feinberg School of Medicine, Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, Illinois 60611, USA.
J Biol Chem. 2011 Jul 15;286(28):24599-607. doi: 10.1074/jbc.M111.235788. Epub 2011 May 23.
Maspin is a non-inhibitory serine protease inhibitor (serpin) that influences many cellular functions including adhesion, migration, and invasion. The underlying molecular mechanisms that facilitate these actions are still being elucidated. In this study we determined the mechanism by which maspin mediates increased MCF10A cell adhesion. Utilizing competition peptides and mutation analyses, we discovered two unique regions (amino acid residues 190-202 and 260-275) involved in facilitating the increased adhesion function of maspin. In addition, we demonstrate that the urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) complex is required for the localization and adhesion function of maspin. Finally, we showed that maspin, uPAR, and β1 integrin co-immunoprecipitate, suggesting a novel maspin-uPA-uPAR-β1 integrin mega-complex that regulates mammary epithelial cell adhesion.
Maspin 是一种非抑制性丝氨酸蛋白酶抑制剂（serpin），它影响多种细胞功能，包括黏附、迁移和侵袭。促进这些作用的潜在分子机制仍在阐明之中。在这项研究中，我们确定了 maspin 介导 MCF10A 细胞黏附增加的机制。利用竞争肽和突变分析，我们发现了两个独特的区域（氨基酸残基 190-202 和 260-275），它们参与促进 maspin 增加黏附的功能。此外，我们证明尿激酶型纤溶酶原激活物（uPA）/uPA 受体（uPAR）复合物是 maspin 定位和黏附功能所必需的。最后，我们表明 maspin、uPAR 和 β1 整合素共免疫沉淀，提示存在一个新的 maspin-uPA-uPAR-β1 整合素巨型复合物，调节乳腺上皮细胞黏附。
