1. Insulin Receptor-Related Receptor as an Extracellular Alkali Sensor
- Author
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Sergey Zozulya, E. B. Burova, Eugenio Bertelli, Pascal Houillier, I. E. Deyev, Dmitry I. Rzhevsky, Arkady N. Murashev, O. V. Serova, Nadezhda V. Popova, Alexander G. Petrenko, Roman G. Efremov, Anastasiya A. Berchatova, Anton O. Chugunov, Dominique Eladari, N. N. Nikolsky, Konstantin P. Vassilenko, and Fabien Sohet
- Subjects
kidney ,insulin receptor-related receptor ,intercalated cells ,alkalosis ,acid-base balance ,Physiology ,Metabolic alkalosis ,Kidney ,Mice ,Xenopus laevis ,0302 clinical medicine ,Phosphorylation ,Receptor ,Mice, Knockout ,Orphan receptor ,0303 health sciences ,Hydrogen-Ion Concentration ,population characteristics ,Signal transduction ,Tyrosine kinase ,Signal Transduction ,medicine.medical_specialty ,Recombinant Fusion Proteins ,Biology ,Article ,Cell Line ,03 medical and health sciences ,Internal medicine ,parasitic diseases ,Extracellular ,medicine ,Animals ,Humans ,Molecular Biology ,Insulin Receptor-Related Receptor ,030304 developmental biology ,Cell Biology ,medicine.disease ,Receptor, Insulin ,Culture Media ,Protein Structure, Tertiary ,Rats ,Mice, Inbred C57BL ,Insulin receptor ,Sodium Bicarbonate ,Endocrinology ,Mutagenesis, Site-Directed ,biology.protein ,Protein Processing, Post-Translational ,030217 neurology & neurosurgery - Abstract
SummaryThe 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.
- Published
- 2011
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