Role of PTP-1B in aortic smooth muscle cell motility and tyrosine phosphorylation of focal adhesion proteins.
Role of PTP-1B in aortic smooth muscle cell motility and tyrosine phosphorylation of focal adhesion proteins.
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PTP-1B 在主动脉平滑肌细胞运动和粘着斑蛋白酪氨酸磷酸化中的作用。
DOI：
10.1152/ajpheart.1999.277.1.h192
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Yao,J
中科院分区：
文献类型：
--
作者：
Hassid,A;Huang,S;Yao,J
最近的研究主要集中在蛋白酪氨酸激酶在血管平滑肌细胞生物学中的作用，但关于蛋白酪氨酸磷酸酶（PTP）的类似信息很少。PTP-1B是一种普遍存在的非受体磷酸酶，其功能不确定，底物大多尚未确定。我们利用反义寡脱氧核苷酸（ODN）对抗PTP-1B，研究内源性PTP-1B在大鼠主动脉平滑肌细胞（RASMC）原代培养细胞运动中的作用。反义ODN以浓度依赖的方式降低PTP-1B蛋白水平和活性，而义、乱序或三碱基错配的反义ODN几乎没有或没有影响。用反义ODN处理细胞，而不是用正、乱序或三碱基错配的反义ODN处理细胞，可以增强细胞活力，增加局灶黏附蛋白paxillin、p130cas和局灶黏附激酶的酪氨酸磷酸化水平。我们的研究结果表明，PTP-1B通过调节几种局灶黏附蛋白中的磷酸酪氨酸水平，是RASMC运动的负调节因子，并表明PTP-1B参与动脉粥样硬化和再狭窄等事件，这些事件与血管平滑肌细胞运动增加有关。
Recent studies have focused attention on the role of protein tyrosine kinases in vascular smooth muscle cell biology, but similar information regarding protein tyrosine phosphatases (PTP) is sparse. PTP-1B is a ubiquitous nonreceptor phosphatase with uncertain function and substrates that are mostly unidentified. We used antisense oligodeoxynucleotides (ODN) against PTP-1B to investigate the role of endogenous PTP-1B in motility of primary cultures of rat aortic smooth muscle cells (RASMC). Antisense ODN decreased PTP-1B protein levels and activity in a concentration-dependent fashion, whereas sense, scrambled, or three-base mismatch antisense ODN had little or no effect. Treatment of cells with antisense ODN, but not sense, scrambled, or three-base mismatch antisense ODN, enhanced cell motility and increased tyrosine phosphorylation levels of focal adhesion proteins paxillin, p130cas, and focal adhesion kinase. Our findings indicate that PTP-1B is a negative regulator of RASMC motility via modulation of phosphotyrosine levels in several focal adhesion proteins and suggest the involvement of PTP-1B in events such as atherosclerosis and restenosis, which are associated with increased vascular smooth muscle cell motility.