Aldosterone interaction with epidermal growth factor receptor signaling in MDCK cells
Aldosterone interaction with epidermal growth factor receptor signaling in MDCK cells
复制标题
DOI：
10.1152/ajprenal.00159.2001
复制
发表时间：
2002-04-01
影响因子：
4.2
通讯作者：
Silbernagl, S
中科院分区：
文献类型：
--
作者：
Gekle, M;Freudinger, R;Silbernagl, S
表皮生长因子(EGF)通过细胞外信号调节激酶(ERK)1/2作为下游信号调控细胞的增殖、分化和离子转运。此外，表皮生长因子受体(EGF-R)通过反式激活参与G蛋白偶联受体、生长激素和细胞因子的信号传递。已有研究表明，类固醇与多肽激素的相互作用部分是通过快速的、潜在的非基因组机制实现的。先前，我们已经证明了醛固酮通过ERK1/2以类似于生长因子的方式调节Madin-Darby犬肾(MDCK)细胞的Na(+)/H(+)交换。在这里，我们验证了一种假设，即在MDCK细胞中，醛固酮使用EGF-R作为异源信号转导。纳摩尔浓度的醛固酮可引起ERK1/2磷酸化、细胞内钙离子浓度和Na(+)/H(+)交换活性的快速增加，与EGF诱导的增加相似。此外，醛固酮诱导EGF-R-Tyr磷酸化迅速增加，抑制EGF-R激酶可阻断醛固酮诱导的信号转导。抑制ERK1/2的磷酸化降低了Ca(2+)的反应，而阻止Ca(2+)内流并不取消ERK1/2的磷酸化。我们的数据显示，醛固酮通过EGF-R-ERK1/2信号通路在MDCK细胞中产生快速效应。
Epidermal growth factor (EGF) regulates cell proliferation, differentiation, and ion transport by using extracellular signal-regulated kinase (ERK)1/2 as a downstream signal. Furthermore, the EGF-receptor (EGF-R) is involved in signaling by G protein-coupled receptors, growth hormone, and cytokines by means of transactivation. It has been suggested that steroids interact with peptide hormones, in part, by rapid, potentially nongenomic, mechanisms. Previously, we have shown that aldosterone modulates Na(+)/H(+) exchange in Madin-Darby canine kidney (MDCK) cells by means of ERK1/2 in a way similar to growth factors. Here, we tested the hypothesis that aldosterone uses the EGF-R as a heterologous signal transducer in MDCK cells. Nanomolar concentrations of aldosterone induce a rapid increase in ERK1/2 phosphorylation, cellular Ca(2+) concentration, and Na(+)/H(+) exchange activity similar to increases induced by EGF. Furthermore, aldosterone induced a rapid increase in EGF-R-Tyr phosphorylation, and inhibition of EGF-R kinase abolished aldosterone-induced signaling. Inhibition of ERK1/2 phosphorylation reduced the Ca(2+) response, whereas prevention of Ca(2+) influx did not abolish ERK1/2 phosphorylation. Our data show that aldosterone uses the EGF-R-ERK1/2 signaling cascade to elicit its rapid effects in MDCK cells.