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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.
Bates,
Insulin receptor-related receptor expression in non-A intercalated cells in the kidney.
1997, Pubmed
Bates,
Insulin receptor-related receptor expression in non-A intercalated cells in the kidney.
1997,
Pubmed Bertelli,
Association between endocrine pancreas and ductal system. More than an epiphenomenon of endocrine differentiation and development?
2005,
Pubmed Chesler,
Regulation and modulation of pH in the brain.
2003,
Pubmed Dandekar,
Comparison of the signaling abilities of the cytoplasmic domains of the insulin receptor and the insulin receptor-related receptor in 3T3-L1 adipocytes.
1998,
Pubmed De Meyts,
Insulin and insulin-like growth factors: the paradox of signaling specificity.
2002,
Pubmed De Meyts,
The insulin receptor: a prototype for dimeric, allosteric membrane receptors?
2008,
Pubmed Deyev,
Regulation of CIRL-1 proteolysis and trafficking.
2010,
Pubmed Dissen,
Expression of the insulin receptor-related receptor is induced by the preovulatory surge of luteinizing hormone in thecal-interstitial cells of the rat ovary.
2006,
Pubmed Dupont,
Insulin and insulin-like growth factor I receptors: similarities and differences in signal transduction.
2001,
Pubmed Eladari,
Rat proximal NHE3 adapts to chronic acid-base disorders but not to chronic changes in dietary NaCl intake.
2002,
Pubmed Flörke,
Hormone-triggered conformational changes within the insulin-receptor ectodomain: requirement for transmembrane anchors.
2001,
Pubmed Hernández-Sánchez,
Evolution of the insulin receptor family and receptor isoform expression in vertebrates.
2008,
Pubmed Hirayama,
Insulin receptor-related receptor is expressed in pancreatic beta-cells and stimulates tyrosine phosphorylation of insulin receptor substrate-1 and -2.
1999,
Pubmed Jui,
Expression of a cDNA encoding the human insulin receptor-related receptor.
1994,
Pubmed Kanzaki,
Insulin receptor signals regulating GLUT4 translocation and actin dynamics.
2006,
Pubmed Kelly-Spratt,
A TrkB/insulin receptor-related receptor chimeric receptor induces PC12 cell differentiation and exhibits prolonged activation of mitogen-activated protein kinase.
1999,
Pubmed Kelly-Spratt,
BDNF activated TrkB/IRR receptor chimera promotes survival of sympathetic neurons through Ras and PI-3 kinase signaling.
2002,
Pubmed Kitamura,
Preserved pancreatic beta-cell development and function in mice lacking the insulin receptor-related receptor.
2001,
Pubmed Klammt,
Comparative analysis of the signaling capabilities of the insulin receptor-related receptor.
2005,
Pubmed Kristensen,
Specificity of insulin and insulin-like growth factor I receptors investigated using chimeric mini-receptors. Role of C-terminal of receptor alpha subunit.
1999,
Pubmed Lawrence,
Insulin receptor structure and its implications for the IGF-1 receptor.
2007,
Pubmed Lou,
The first three domains of the insulin receptor differ structurally from the insulin-like growth factor 1 receptor in the regions governing ligand specificity.
2006,
Pubmed Ma,
Molecular characterization of the TrkA/NGF receptor minimal enhancer reveals regulation by multiple cis elements to drive embryonic neuron expression.
2000,
Pubmed Mathi,
Insulin receptor-related receptor messenger ribonucleic acid: quantitative distribution and localization to subpopulations of epithelial cells in stomach and kidney.
1995,
Pubmed McKern,
Structure of the insulin receptor ectodomain reveals a folded-over conformation.
2006,
Pubmed Nef,
Testis determination requires insulin receptor family function in mice.
2003,
Pubmed Niemeyer,
Neutralization of a single arginine residue gates open a two-pore domain, alkali-activated K+ channel.
2007,
Pubmed Niv,
The alkaline tide phenomenon.
2002,
Pubmed Ozaki,
Insulin receptor-related receptor in rat islets of Langerhans.
1998,
Pubmed Ozaki,
Localization of insulin receptor-related receptor in the rat kidney.
1997,
Pubmed Purkerson,
Adaptation to metabolic acidosis and its recovery are associated with changes in anion exchanger distribution and expression in the cortical collecting duct.
2010,
Pubmed Quentin,
Regulation of the Cl-/HCO3- exchanger AE2 in rat thick ascending limb of Henle's loop in response to changes in acid-base and sodium balance.
2004,
Pubmed Quentin,
The Cl-/HCO3- exchanger pendrin in the rat kidney is regulated in response to chronic alterations in chloride balance.
2004,
Pubmed Rentería,
A comparative structural bioinformatics analysis of the insulin receptor family ectodomain based on phylogenetic information.
2008,
Pubmed Royaux,
Pendrin, encoded by the Pendred syndrome gene, resides in the apical region of renal intercalated cells and mediates bicarbonate secretion.
2001,
Pubmed Sabolić,
Regulation of AE1 anion exchanger and H(+)-ATPase in rat cortex by acute metabolic acidosis and alkalosis.
1997,
Pubmed Schwartz,
Plasticity of functional epithelial polarity.
,
Pubmed Shier,
Primary structure of a putative receptor for a ligand of the insulin family.
1989,
Pubmed Sparrow,
The disulfide bonds in the C-terminal domains of the human insulin receptor ectodomain.
1997,
Pubmed Srivastava,
Intracellular pH sensors: design principles and functional significance.
2007,
Pubmed Tsujimoto,
Insulin receptor-related receptor messenger ribonucleic acid in the stomach is focally expressed in the enterochromaffin-like cells.
1995,
Pubmed Ullrich,
Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity.
1986,
Pubmed Ullrich,
Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes.
,
Pubmed Wagner,
Regulation of the expression of the Cl-/anion exchanger pendrin in mouse kidney by acid-base status.
2002,
Pubmed Wall,
Recent advances in our understanding of intercalated cells.
2005,
Pubmed Ward,
The three dimensional structure of the type I insulin-like growth factor receptor.
2001,
Pubmed Zhang,
The insulin receptor-related receptor. Tissue expression, ligand binding specificity, and signaling capabilities.
1992,
Pubmed
