Acute Downregulation of ENaC by EGF Involves the PY Motif and Putative ERK Phosphorylation Site

上皮钠通道 肾钠重吸收 MAPK/ERK通路 表皮生长因子 重吸收 磷酸化 化学 细胞外 分子生物学 激酶 内分泌学 内科学 细胞生物学 生物 生物化学 医学 受体 有机化学
作者
Rebecca A. Falin,Calvin U. Cotton
出处
期刊:The Journal of General Physiology [Rockefeller University Press]
卷期号:130 (3): 313-328 被引量:43
标识
DOI:10.1085/jgp.200709775
摘要

The epithelial sodium channel (ENaC) is expressed in a variety of tissues, including the renal collecting duct, where it constitutes the rate-limiting step for sodium reabsorption. Liddle's syndrome is caused by gain-of-function mutations in the β and γ subunits of ENaC, resulting in enhanced Na reabsorption and hypertension. Epidermal growth factor (EGF) causes acute inhibition of Na absorption in collecting duct principal cells via an extracellular signal–regulated kinase (ERK)–dependent mechanism. In experiments with primary cultures of collecting duct cells derived from a mouse model of Liddle's disease (β-ENaC truncation), it was found that EGF inhibited short-circuit current (Isc) by 24 ± 5% in wild-type cells but only by 6 ± 3% in homozygous mutant cells. In order to elucidate the role of specific regions of the β-ENaC C terminus, Madin-Darby canine kidney (MDCK) cell lines that express β-ENaC with mutation of the PY motif (P616L), the ERK phosphorylation site (T613A), and C terminus truncation (R564stop) were created using the Phoenix retroviral system. All three mutants exhibited significant attenuation of the EGF-induced inhibition of sodium current. In MDCK cells with wild-type β-ENaC, EGF-induced inhibition of Isc (<30 min) was fully reversed by exposure to an ERK kinase inhibitor and occurred with no change in ENaC surface expression, indicative of an effect on channel open probability (Po). At later times (>30 min), EGF-induced inhibition of Isc was not reversed by an ERK kinase inhibitor and was accompanied by a decrease in ENaC surface expression. Our results are consistent with an ERK-mediated decrease in ENaC open probability and enhanced retrieval of sodium channels from the apical membrane.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
Tina完成签到 ,获得积分10
1秒前
little完成签到,获得积分10
1秒前
3dyf完成签到,获得积分10
2秒前
LU41完成签到,获得积分10
5秒前
6秒前
无奈的代珊完成签到 ,获得积分10
7秒前
8秒前
拉长的断天完成签到,获得积分10
8秒前
科研通AI5应助doin采纳,获得10
9秒前
zho发布了新的文献求助10
9秒前
9秒前
9秒前
七月发布了新的文献求助10
11秒前
11秒前
12秒前
香蕉觅云应助liuliu采纳,获得10
12秒前
顺心修洁完成签到,获得积分10
13秒前
贺小刚发布了新的文献求助10
13秒前
14秒前
sibo完成签到,获得积分10
15秒前
zho发布了新的文献求助10
15秒前
自觉紫安发布了新的文献求助10
18秒前
18秒前
kokaine完成签到,获得积分10
19秒前
孤独的珩完成签到,获得积分10
19秒前
夏子天咿呀咿呀哟完成签到,获得积分10
20秒前
direct完成签到,获得积分10
21秒前
21秒前
21秒前
小猪坨完成签到,获得积分10
21秒前
22秒前
花椒鱼完成签到 ,获得积分10
22秒前
23秒前
独特语琴完成签到,获得积分20
24秒前
玛卡巴卡发布了新的文献求助10
24秒前
zhxia发布了新的文献求助10
26秒前
26秒前
28秒前
28秒前
31秒前
高分求助中
Les Mantodea de Guyane Insecta, Polyneoptera 2500
Mobilization, center-periphery structures and nation-building 600
Technologies supporting mass customization of apparel: A pilot project 450
China—Art—Modernity: A Critical Introduction to Chinese Visual Expression from the Beginning of the Twentieth Century to the Present Day 430
Tip60 complex regulates eggshell formation and oviposition in the white-backed planthopper, providing effective targets for pest control 400
A Field Guide to the Amphibians and Reptiles of Madagascar - Frank Glaw and Miguel Vences - 3rd Edition 400
China Gadabouts: New Frontiers of Humanitarian Nursing, 1941–51 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3793333
求助须知:如何正确求助?哪些是违规求助? 3338077
关于积分的说明 10288655
捐赠科研通 3054718
什么是DOI,文献DOI怎么找? 1676139
邀请新用户注册赠送积分活动 804145
科研通“疑难数据库(出版商)”最低求助积分说明 761757