PAI-1 inhibits urokinase-induced chemotaxis by internalizing the urokinase receptor

被引：63

作者：

Degryse, B ^{[1
]}

Sier, CFM ^{[1
]}

Resnati, M ^{[1
]}

Conese, M ^{[1
]}

Blasi, F ^{[1
]}

机构：

[1] Univ Vita Salute San Raffaele, Dept Cell Biol & Funct Genet, DIBIT, Mol Genet Unit, I-20132 Milan, Italy

来源：

FEBS LETTERS | 2001年 / 505卷 / 02期

关键词：

D O I：

10.1016/S0014-5793(01)02797-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

PAI-1 (plasminogen activator inhibitor-1) binds the urokinase-type plasminogen activator (uPA) and causes its degradation via its receptor uPAR and low-density lipoprotein receptor-related protein (LRP). While both uPA and PAI-1 are chemoattractants, we find that a preformed uPA-PAI-1 complex has no chemotactic activity and that PAI-1 inhibits uPA-induced chemotaxis. The inhibitory effect of PAI-1 on uPA-dependent chemotaxis is reversed when uPAR internalization is inhibited by the 39 kDa receptor-associated protein or by anti-LRP antibodies. Under the same conditions, the uPA-PAI-1 complex is turned into a chemoattractant causing cytoskeleton reorganization and extracellular-regulated kinase/mitogen-activated protein kinases activation. Thus, uPAR internalization by PAI-1 regulates cell migration. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

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收藏

页码：249 / 254

页数：6

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