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标题：Csk-Induced Phosphorylation of Src at Tyrosine 530 is Essential for H₂O₂-Mediated Suppression of ERK1/2 in Human Umbilical Vein Endothelial Cells
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作者：Bo Kyung Jeon ; Kihwan Kwon ; Jihee Lee Kang 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
DOI：10.1038/srep12725
出版社：Springer Nature
摘要：Mitogen-activated protein kinases (MAPKs) are key signal transducers involved in various cellular events such as growth, proliferation, and differentiation. Previous studies have reported that H₂O₂ leads to phosphorylation of extracellular signal-regulated kinase (ERK), one of the MAPKs in endothelial cells. The current study shows that H₂O₂ suppressed ERK1/2 activation and phosphorylation at specific concentrations and times in human umbilical vein endothelial cells but not in immortalized mouse aortic endothelial cells or human astrocytoma cell line CRT-MG. Phosphorylation of other MAPK family members (i.e., p38 and JNK) was not suppressed by H₂O₂. The decrease in ERK1/2 phosphorylation induced by H₂O₂ was inversely correlated with the level of phosphorylation of Src tyrosine 530. Using siRNA, it was found that H₂O₂-induced suppression of ERK1/2 was dependent on Csk. Physiological laminar flow abrogated, but oscillatory flow did not affect, the H₂O₂-induced suppression of ERK1/2 phosphorylation. In conclusion, H₂O₂-induced Csk translocation to the plasma membrane leads to phosphorylation of Src at the tyrosine 530 residue resulting in a reduction of ERK1/2 phosphorylation. Physiological laminar flow abrogates this effect of H₂O₂ by inducing phosphorylation of Src tyrosine 419. These findings broaden our understanding of signal transduction mechanisms in the endothelial cells against oxidative stress.