Laboratory of Receptor Cell Biology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Cell Metab. 2011 Jun 8;13(6):679-89. doi: 10.1016/j.cmet.2011.03.022.
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 and 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.
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 值>7.9 的碱性介质中均可被激活。IRR 的碱感应特性在青蛙、小鼠和人类中是保守的。IRR 的激活是特异性的、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引发细胞内信号转导。IRR 的 pH 敏感性主要由其 L1F 细胞外结构域决定。IRR 主要表达在与碱性介质接触的器官中。特别是，IRR 在分泌碳酸氢盐进入尿液的肾脏细胞亚群中表达。在小鼠中破坏 IRR 会损害肾脏对碱负荷的反应，表现为代谢性碱中毒的发展和对这种挑战的尿碳酸氢盐排泄减少。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多。
