title: Csk-Induced Phosphorylation of Src at Tyrosine 530 is Essential for H2O2-Mediated Suppression of ERK1/2 in Human Umbilical Vein Endothelial Cells.
abstract: 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.
authors.affiliation: 1] Department of Physiology, School of Medicine, Ewha Womans University, Seoul, Korea [2] Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Bo Kyung
authors.initials: BK
authors.lastname: Jeon
authors.affiliation: Department of Internal Medicine, Division of Cardiology, School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Kihwan
authors.initials: K
authors.lastname: Kwon
authors.affiliation: 1] Department of Physiology, School of Medicine, Ewha Womans University, Seoul, Korea [2] Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Jihee Lee
authors.initials: JL
authors.lastname: Kang
authors.affiliation: 1] Department of Physiology, School of Medicine, Ewha Womans University, Seoul, Korea [2] Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Youn-Hee
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000818:Animals; D017209:Apoptosis; D000081247:CSK Tyrosine-Protein Kinase; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D034741:RNA, Small Interfering; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D014443:Tyrosine; D006861:Hydrogen Peroxide; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048670:MAP Kinase Kinase 4