Mitogen-activated protein kinase phosphatase-1 in rat arterial smooth muscle cell proliferation
Mitogen-activated protein kinase phosphatase-1 in rat arterial smooth muscle cell proliferation
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DOI：
10.1172/jci118949
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发表时间：
1996-10-01
影响因子：
15.9
通讯作者：
Haber, E
中科院分区：
文献类型：
--
作者：
Lai, KH;Wang, H;Haber, E
血管平滑肌细胞的增殖和迁移在动脉硬化中起重要作用。在这个过程中，细胞因子和生长因子被上调，并与它们各自的受体结合，进而刺激丝裂原激活蛋白(MAP)激酶。然后，MAP激酶将激活静止的平滑肌细胞的信号传递到细胞核。磷酸酶下调MAP激酶的表达。我们研究了一种双特异性酪氨酸磷酸酶--MKP-1在平滑肌细胞增殖中的作用。Northern分析显示MKP-1在动脉组织中高表达，原位杂交检测到MKP-1主要在动脉平滑肌层表达。大鼠颈动脉球囊损伤后，MKP-1的表达显著降低，而MAP激酶，尤其是p44 MAP激酶的表达明显增加，MKP-1的表达减少的时间进程与酪氨酸磷酸化增强和P44 MAP激酶酶活性升高有关。在高表达MKP-1的大鼠动脉平滑肌细胞中，生长受阻于G1期，进入S期受阻，MKP-1的表达减少可能是血管损伤后平滑肌细胞增殖的部分原因，可能是通过减少p44 MAP激酶的去磷酸化。
Smooth muscle cell proliferation and migration is important in arteriosclerosis. In this process, cytokines and growth factors are upregulated and bind to their respective receptors, which in turn stimulate mitogen-activated protein (MAP) kinases. MAP kinases then relay signals to the nucleus that activate quiescent smooth muscle cells. Phosphatases downregulate MAP kinases. We investigated the role of a dual-specificity tyrosine phosphatase, MAP kinase phosphatase-1 (MKP-1), in smooth muscle cell proliferation. MKP-1 expression was high in arterial tissue by Northern analysis, and MKP-1 message was detected mainly in the arterial smooth muscle layer by in situ hybridization. After balloon injury of the rat carotid artery, expression of MKP-1 decreased greatly, whereas that of MAP kinases, especially p44 MAP kinase, increased, The time course of the reduction in MKP-1 message correlated with increased tyrosine phosphorylation and elevated p44 MAP kinase enzymatic activity. In rat arterial smooth muscle cells overexpressing MKP-1, growth was arrested in the G1 phase and entry into the S phase was blocked, A reduction in MKP-1 expression may contribute in part to proliferation of smooth muscle cells after vascular injury, possibly through a decrease in dephosphorylation of p44 MAP kinase.