砷和砷酸激活细胞外signal-regulated激酶1/2的表皮生长因子受体介导途径正常的人类角质细胞。
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Tanaka-Kagawa T, Hanioka N,吉田H, Jinno H,安藤M
砷和砷酸激活细胞外signal-regulated激酶1/2的表皮生长因子受体介导途径正常的人类角质细胞。
Br北京医学。2003年12月,149(6):1116 - 27所示。
- PubMed ID
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14674888 (在PubMed]
- 文摘
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背景:无机砷是一种环境污染物,并与人类皮肤癌的风险增加有关。砷报道激活或抑制多种细胞信号通路对细胞生长的影响,分化和细胞凋亡。然而,这些arsenic-induced生物效应的分子机制并不完全清楚。目标:了解的分子基础的行动方式,偏方我们检查了亚砷酸盐的作用,砷酸增殖激活的蛋白激酶(MAPK)和正常的人类表皮角化细胞的上游信号级联(这些)。方法:这些被暴露于亚砷酸盐或砷酸。免疫印迹分析确定激活细胞外signal-regulated激酶(ERK) 1/2, c-jun n端激酶(物),p38和MAPK或ERK激酶(MEK) 1/2。表皮生长因子受体(EGFR)酪氨酸磷酸化和招聘的适配器蛋白质,人体自燃和Grb2 EGFR被检测到免疫沉淀反应和免疫印迹分析。结果:两种激活ERK1/2偏方,最高能够激活促有丝分裂的刺激,除了物和p38反应中表现出更大的激活细胞的压力。的动力学ERK1/2激活不同于物和p38激活。前两个偏方ERK1/2期间短暂地激活物和p38激活。 MEK1/2, upstream kinases of ERK1/2, were also activated by arsenicals with similar time kinetics to that of ERK1/2 activation. To investigate a signalling pathway leading to activation of MEK1/2-ERK1/2, we examined the tyrosine phosphorylation of EGFR and Shc adapter protein. Both arsenicals stimulated tyrosine phosphorylation of EGFR and Shc. After arsenical treatment, Shc immunoprecipitates contained coprecipitated EGFR and Grb2, suggesting that both arsenicals induce the assembly of EGFR-Shc-Grb2 complexes. Both the EGFR inhibitor tyrphostin AG1478 and anti-EGFR blocking antibody markedly attenuated ERK1/2 activation induced by arsenicals, but did not affect JNK and p38 activation. CONCLUSIONS: Our data indicate that both arsenite and arsenate activate the EGFR-Shc-Grb2-MEK1/2-ERK1/2 signalling cascade in NHEK.