Insulin receptor-related receptor as an extracellular alkali sensor.
Insulin receptor-related receptor as an extracellular alkali sensor.
复制标题
DOI：
10.1016/j.cmet.2011.03.022
复制
发表时间：
2011-06-08
期刊：
影响因子：
29
通讯作者：
Petrenko AG
中科院分区：
文献类型：
--
作者：
Deyev IE;Sohet F;Vassilenko KP;Serova OV;Popova NV;Zozulya SA;Burova EB;Houillier P;Rzhevsky DI;Berchatova AA;Murashev AN;Chugunov AO;Efremov RG;Nikol'sky NN;Bertelli E;Eladari D;Petrenko AG
胰岛素受体相关受体（IRR）是胰岛素受体家族的孤儿受体酪氨酸激酶，在体外和体内pH>7.9时均可被碱性介质激活。IRR的碱敏感特性在青蛙、小鼠和人类中是保守的。IRR激活是特异性的、剂量依赖性的、快速可逆的，并表现出正协同性。它还触发受体构象变化并增强细胞内信号传导。IRR的pH敏感性主要由其L1F胞外结构域定义。IRR主要在与弱碱性培养基接触的器官中表达。特别地，IRR在将碳酸氢盐分泌到尿液中的肾脏细胞亚群中表达。小鼠IRR的破坏损害了肾脏对碱负荷的反应，这通过代谢性肾功能衰竭的发生和响应于该挑战的尿碳酸氢盐排泄减少来证明。因此，我们假设IRR是一种碱传感器，在肾脏中发挥作用，以管理代谢性碳酸氢盐过量。
The insulin receptor-related receptor (IRR), an orphan receptor tyrosine kinase of the insulin receptor family, can be activated by alkaline media both in vitro and in vivo at pH>7.9. The alkali-sensing property of IRR is conserved in frog, mouse and human. IRR activation is specific, dose-dependent, quickly reversible and demonstrates positive cooperativity. It also triggers receptor conformational changes and elicits intracellular signaling. The pH sensitivity of IRR is primarily defined by its L1F extracellular domains. IRR is predominantly expressed in organs that come in contact with mildly alkaline media. In particular, IRR is expressed in the cell subsets of the kidney that secrete bicarbonate into urine. Disruption of IRR in mice impairs the renal response to alkali loading attested by development of metabolic alkalosis and decreased urinary bicarbonate excretion in response to this challenge. We therefore postulate that IRR is an alkali sensor that functions in the kidney to manage metabolic bicarbonate excess.
登录
查看更多内容
影响因子：
4.8
作者：
MATHI, SK;CHAN, J;WATT, VM
通讯作者：
WATT, VM
影响因子：
4.8
作者：
Dissen, GA;Garcia-Rudaz, C;Ojeda, SR
通讯作者：
Ojeda, SR
影响因子：
64.8
作者：
McKern, Neil M.;Lawrence, Michael C.;Ward, Colin W.
通讯作者：
Ward, Colin W.
DOI：
10.1152/ajprenal.00188.2001
发表时间：
2002-05-01
影响因子：
4.2
作者：
Eladari, D;Leviel, F;Chambrey, R
通讯作者：
Chambrey, R
影响因子：
5.3
作者：
Kitamura, T;Kido, Y;Accili, D
通讯作者：
Accili, D