Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) is involved in the activation of endothelial Integrins
Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) is involved in the activation of endothelial Integrins
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DOI：
10.1002/jcp.10169
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发表时间：
2002-11-01
影响因子：
5.6
通讯作者：
Sato, Y
中科院分区：
文献类型：
--
作者：
Akada, T;Yamazaki, T;Sato, Y
我们先前报道了嘌呤霉素不敏感的亮氨酰特异性氨基肽酶（mPILSAP）的小鼠直向同源物通过调节内皮细胞（EC）的增殖和迁移在血管生成中起重要作用（Miyashita等人，2002. Blood 99：3241-3249）。在这里，我们研究了mPILSAP如何调节EC迁移的机制。通过整联蛋白的细胞粘附在细胞迁移中起关键作用，并且EC至少使用1型胶原受体整联蛋白α 2 β 1、纤连蛋白受体α 5 β 1和玻连蛋白受体α v β 3和α v β 5。mPILSAP反义寡脱氧核苷酸（AS-ODN）或亮氨酰氨肽酶抑制剂亮氨酸硫醇（LT）不影响小鼠内皮细胞系MSS 31的细胞的附着，但当它们铺在玻连蛋白-、纤连蛋白-或1型胶原上时，它们确实显著抑制了细胞的铺展，尽管它们不影响整合素α 2、α 5、α v、β 1、β 3、和β 5亚基。AS-ODN和LT也抑制FAK的酪氨酸磷酸化，当细胞接种在玻连蛋白，纤连蛋白，或1型胶原。Mg ~（2+）可抑制细胞铺展和FAK酪氨酸磷酸化。这些结果表明mPILSAP参与内皮整合素的活化。(C)2002 Wiley-Liss，Inc.
We previously reported that mouse orthologue of puromycin insensitive leucyl-specific aminopeptidase (mPILSAP) played an important role in angiogenesis by regulating the proliferation and migration of endothelial cells (ECs) (Miyashita et al., 2002. Blood 99:3241-3249). Here, we examined the mechanism as to how mPILSAP regulates the migration of ECs. Cell adhesion through integrins plays a crucial role in cell migration, and ECs use at least type-1 collagen receptor integrin alpha2beta1, fibronectin receptor alpha5beta1, and vitronectin receptors alphavbeta3 and alphavbeta5. mPILSAP antisense oligodeoxynucleotide (AS-ODN) or leucinethiol (LT), a leucyl-aminopeptidase inhibitor, did not affect the attachment but did significantly inhibit the spreading of cells of the murine endothelial cell line MSS31 when they were plated on vitronectin-, fibronectin-, or type-1 collagen, although they did not affect the expression of integrin alpha2, alpha5, alphav, beta1, beta3, and beta5 subunits on the cell surface. AS-ODN and LT also inhibited the tyrosine phosphorylation of FAK when cells were plated on vitronectin, fibronectin, or type-1 collagen. This inhibition of cell spreading and of tyrosine phosphorylation of FAK could be negated by Mg2+. These results suggest that mPILSAP is involved in the activation of endothelial integrins. (C) 2002 Wiley-Liss, Inc.