Tyrosine kinase activity of discoidin domain receptor 1 is necessary for smooth muscle cell migration and matrix metalloproteinase expression
Tyrosine kinase activity of discoidin domain receptor 1 is necessary for smooth muscle cell migration and matrix metalloproteinase expression
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DOI：
10.1161/01.res.0000022166.74073.f8
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发表时间：
2002-06-14
影响因子：
20.1
通讯作者：
Bendeck, MP
中科院分区：
文献类型：
--
作者：
Hou, GP;Vogel, WF;Bendeck, MP
平滑肌细胞（SMC）与胶原蛋白的相互作用介导了动脉粥样硬化和再狭窄发病过程中的细胞迁移。盘状蛋白结构域受体（disidin domain receptor, DDRs）是一种新的胶原受体。我们使用野生型和DDR1（-/-）小鼠的主动脉SMCs来评估DDR1在调节迁移中的功能。DDR1(-/-) SMCs表现出对I型胶原底物的粘附和迁移受损。基质金属蛋白酶-2 （MMP-2）和MMP-9活性同时降低。转染DDR1b全长cDNA修复了这些缺陷，而DDR1的激酶死亡突变体恢复了附着，但没有迁移和MMP的产生。这些结果表明，活性DDR1激酶是SMC迁移的中心介质。
Smooth muscle cell (SMC) interactions with collagen mediate cell migration during the pathogenesis of atherosclerosis and restenosis. Discoidin domain receptors (DDRs) have been identified as novel collagen receptors. We used aortic SMCs from wild-type and DDR1(-/-) mice to evaluate the function of the DDR1 in regulating migration. DDR1(-/-) SMCs exhibited impaired attachment to and migration toward a type I collagen substrate. Matrix metalloproteinase-2 (MMP-2) and MMP-9 activities were concomitantly reduced in these cells. Transfection of a full-length cDNA for DDR1b rescued these deficits, whereas kinase-dead mutants of DDR1 restored attachment but not migration and MMP production. These results suggest that active DDR1 kinase is a central mediator of SMC migration.