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Insulin receptor-related receptor as an extracellular alkali sensor.

Authors: 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 
Citation: Deyev IE, etal., Cell Metab. 2011 Jun 8;13(6):679-89. doi: 10.1016/j.cmet.2011.03.022.
Pubmed: (View Article at PubMed) PMID:21641549
DOI: Full-text: 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.


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CRRD Object Information
CRRD ID: 8554627
Created: 2014-05-08
Species: All species
Last Modified: 2014-05-08
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.