Mechanical pressure-induced phosphorylation of p38 mitogen-activated protein kinase in epithelial cells via Src and protein kinase C.
Mechanical pressure-induced phosphorylation of p38 mitogen-activated protein kinase in epithelial cells via Src and protein kinase C.
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DOI：
10.1016/j.bbrc.2004.02.101
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发表时间：
2004-04
影响因子：
3.1
通讯作者：
M. Hofmann;Julijana Zaper;A. Bernd;J. Bereiter-Hahn;R. Kaufmann;S. Kippenberger
中科院分区：
文献类型：
--
作者：
M. Hofmann;Julijana Zaper;A. Bernd;J. Bereiter-Hahn;R. Kaufmann;S. Kippenberger
已知机械刺激调节多种不同组织中的细胞生理学。特别地，上皮细胞永久地暴露于由外部施加的力产生的机械刺激。本体外研究表明，机械压力作为上皮细胞中p38丝裂原活化蛋白激酶（MAPK）通路的一个因子。机械压力（1.02g/cm ~ 2）导致p38快速磷酸化，峰值在5 ~ 10 min之间。此外，磷酸化的小热休克蛋白27（HSP 27）显示在响应机械压力。通过使用特异性抑制剂抑制p38功能，阻断了压力介导的HSP 27磷酸化。为了确定p38的上游调节因子，研究了Src和蛋白激酶C（PKC）在压力信号传导中的贡献。我们可以证明，Src或PKC抑制压力诱导的p38磷酸化。这些研究结果表明，机械压力作为一种新型的效应刺激p38通路的影响（病理）生理条件。
Mechanical stimulation is known to modulate cell physiology in a variety of different tissues. Particularly, epithelial cells are permanently exposed to mechanical stimulation generated by externally applied forces. The present in vitro study demonstrated mechanical pressure as a trigger-factor of the p38 mitogen-activated protein kinase (MAPK) pathway in epithelial cells. Mechanical pressure applied by teflon weights (1.02g/cm2) led to a rapid phosphorylation of p38 peaking between 5 and 10min. Furthermore, phosphorylation of the small heat shock protein 27 (HSP27) was shown in response to mechanical pressure. Suppression of p38 function by using specific inhibitors blocked the pressure-mediated phosphorylation of HSP27. In order to identify upstream regulators of p38, a contribution of Src and protein kinase C (PKC) in pressure-signaling was investigated. We could demonstrate that inhibition of Src or PKC suppressed the pressure-induced phosphorylation of p38. These findings suggest mechanical pressure as a new type of effector stimulus for the p38 pathway with implications to (patho-) physiological conditions.