The serpin PAI-1 inhibits cell migration by blocking integrin alpha(v)beta(3) binding to vitronectin

被引:601
|
作者
Stefansson, S [1 ]
Lawrence, DA [1 ]
机构
[1] AMER RED CROSS,JEROME H HOLLAND LAB,DEPT BIOCHEM,ROCKVILLE,MD 20855
关键词
D O I
10.1038/383441a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
DURING wound healing, migrating cells increase expression of both the vitronectin receptor (VNR) integrins(1) and plasminogen activators(2,3). Here we report that vitronectin significantly enhances the migration of smooth muscle cells (SMCs), and that the specific VNR alpha(v) beta(3) is required for cell motility, We also show that the alpha(v) beta(3) attachment site on vitronectin overlaps with the binding site for plasminogen activator inhibitor (PAI)-1, and that the active conformation of PAI-I blocks SMC migration, This effect requires high-affinity binding to vitronectin, and is not dependent on the ability of PAI-1 to inhibit plasminogen activators. Formation of a complex between PAI-1 and plasminogen activators results in loss of PAI-1 affinity for vitronectin and restores cell migration. These data demonstrate a direct link between plasminogen activators and integrin-mediated cell migration, and show that PAI-1 can control cell-matrix interactions by regulating the accessibility of specific cell-attachment sites. This indicates that the localization of plasminogen activators at sites of focal contact does not initiate a proteolytic cascade leading to generalized matrix destruction, but instead is required to expose cryptic cell-attachment sites necessary for SMC migration.
引用
收藏
页码:441 / 443
页数:3
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