Plk1 regulates MEK1/2 and proliferation in airway smooth muscle cells.
Plk1 regulates MEK1/2 and proliferation in airway smooth muscle cells.
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DOI：
10.1186/s12931-015-0257-8
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发表时间：
2015-08-05
影响因子：
5.8
通讯作者：
Tang DD
中科院分区：
文献类型：
--
作者：
Jiang S;Tang DD
polo样激酶1 （Plk1）是一种丝氨酸/苏氨酸蛋白激酶，参与有丝分裂的调节。此外，丝裂原活化蛋白激酶（MAPK）的激活是生长因子反应早期的关键事件。Plk1在细胞中MAPK磷酸化中的作用尚未被研究。利用免疫印迹分析评估血小板衍生生长因子（PDGF）刺激后细胞中Plk1和MAPK的磷酸化情况。我们还生成了稳定的Plk1敲低（KD）细胞，以评估Plk1在MAPK激活和细胞增殖中的作用。此外，我们使用了一个不可磷酸化的Plk1突变体来确定Plk1磷酸化在这些过程中的功能。PDGF处理增加了人气道平滑肌细胞中Plk1在Thr-210位点的磷酸化（Plk1激活的指示）。Plk1 KD可减弱pdgf诱导的MEK1/2和ERK1/2磷酸化以及细胞增殖。然而，PDGF刺激后，Plk1 KD细胞中Raf-1和AKT的磷酸化并未降低。此外，T210A Plk1 （Thr-210的丙氨酸取代）的表达抑制了pdgf刺激的MEK1/2磷酸化、ERK1/2磷酸化和细胞增殖。综上所述，这些发现表明Plk1在生长因子刺激下被激活，这可能控制了MEK1/2和ERK1/2的激活，以及平滑肌细胞的增殖。
Polo-like kinase 1 (Plk1) is a serine/threonine protein kinase that has been implicated in the regulation of mitosis. In addition, the activation of mitogen-activated protein kinase (MAPK) is a key event in the early stage of the growth factor response. The role of Plk1 in MAPK phosphorylation in cells has not been investigated. Immunoblot analysis was used to evaluate Plk1 and MAPK phosphorylation in cells upon stimulation with platelet-derived growth factor (PDGF). We also generated stable Plk1 knockdown (KD) cells to assess the role of Plk1 in MAPK activation and cell proliferation. Furthermore, we used a non-phosphorylatable Plk1 mutant to determine the function of Plk1 phosphorylation in these processes. Treatment with PDGF increased Plk1 phosphorylation at Thr-210 (an indication of Plk1 activation) in human airway smooth muscle cells. Plk1 KD attenuated the PDGF-induced phosphorylation of MEK1/2 and ERK1/2 as well as cell proliferation. However, phosphorylation of Raf-1 and AKT upon stimulation with PDGF was not reduced in Plk1 KD cells. Furthermore, the expression of T210A Plk1 (alanine substitution at Thr-210) inhibited the PDGF-stimulated MEK1/2 phosphorylation, ERK1/2 phosphorylation and cell proliferation. Together, these findings suggest that Plk1 is activated upon growth factor stimulation, which may control the activation of MEK1/2 and ERK1/2, and smooth muscle cell proliferation.