calcium sensing receptor


Gene Symbol: calcium sensing receptor
Description: calcium sensing receptor
Alias: CAR, EIG8, FHH, FIH, GPRC2A, HHC, HHC1, HYPOC1, NSHPT, PCAR1, hCasR, extracellular calcium-sensing receptor, parathyroid Ca(2+)-sensing receptor 1, parathyroid cell calcium-sensing receptor 1
Species: human
Products:     calcium sensing receptor

Top Publications

  1. Awata H, Huang C, Handlogten M, Miller R. Interaction of the calcium-sensing receptor and filamin, a potential scaffolding protein. J Biol Chem. 2001;276:34871-9 pubmed identify proteins that might organize the signaling system(s) activated by the extracellular Ca(2+) receptor (CaR), we used a bait construct representing the intracellular C terminus of the human CaR and the yeast two hybrid ..
  2. Schwartz G, John E, Rowland G, Ingles S. Prostate cancer in African-American men and polymorphism in the calcium-sensing receptor. Cancer Biol Ther. 2010;9:994-9 pubmed
    ..The CaSR Q1011E minor allele, which is common in populations with African ancestry, may be associated with a less aggressive form of prostate cancer among African-American men. ..
  3. Freichel M, Zink Lorenz A, Holloschi A, Hafner M, Flockerzi V, Raue F. Expression of a calcium-sensing receptor in a human medullary thyroid carcinoma cell line and its contribution to calcitonin secretion. Endocrinology. 1996;137:3842-8 pubmed
    ..This receptor contributes not only to the inhibition of PTH secretion in the parathyroid, but also to the stimulation of calcitonin secretion in C cells. ..
  4. Kapur K, Johnson T, Beckmann N, Sehmi J, Tanaka T, Kutalik Z, et al. Genome-wide meta-analysis for serum calcium identifies significantly associated SNPs near the calcium-sensing receptor (CASR) gene. PLoS Genet. 2010;6:e1001035 pubmed publisher
    ..This study highlights the key role of CASR in calcium regulation. ..
  5. Quinn S, Kifor O, Trivedi S, Diaz R, Vassilev P, Brown E. Sodium and ionic strength sensing by the calcium receptor. J Biol Chem. 1998;273:19579-86 pubmed
    The calcium-sensing receptor (CaR) is activated by small changes in extracellular calcium [Ca2+]o) in the physiological range, allowing the parathyroid gland to regulate serum [Ca2+]o; however, the CaR is also distributed in a number of ..
  6. Dong L, Ulrich C, Hsu L, Duggan D, Benitez D, White E, et al. Genetic variation in calcium-sensing receptor and risk for colon cancer. Cancer Epidemiol Biomarkers Prev. 2008;17:2755-65 pubmed publisher
    ..Nonetheless, these findings require confirmation. ..
  7. Bu L, Michino M, Wolf R, Brooks C. Improved model building and assessment of the Calcium-sensing receptor transmembrane domain. Proteins. 2008;71:215-26 pubmed
    ..This provides validation of our sequence alignment method and the use of the rhodopsin backbone as the initial structure in homology modeling of other G protein-coupled receptors that are not members of the rhodopsin family. ..
  8. Canaff L, Hendy G. Human calcium-sensing receptor gene. Vitamin D response elements in promoters P1 and P2 confer transcriptional responsiveness to 1,25-dihydroxyvitamin D. J Biol Chem. 2002;277:30337-50 pubmed
    ..In summary, functional VDREs have been identified in the CASR gene and provide the mechanism whereby 1,25(OH)2D up-regulates parathyroid, thyroid C-cell, and kidney CASR expression. ..
  9. Tu C, Chang W, Bikle D. The role of the calcium sensing receptor in regulating intracellular calcium handling in human epidermal keratinocytes. J Invest Dermatol. 2007;127:1074-83 pubmed
    ..We previously reported that the calcium sensing receptor (CaR) is required for mediating Ca2+ signaling and extracellular Ca2+ (Ca2+(o))-induced differentiation...

More Information

Publications102 found, 100 shown here

  1. Mun H, Franks A, Culverston E, Krapcho K, Nemeth E, Conigrave A. The Venus Fly Trap domain of the extracellular Ca2+ -sensing receptor is required for L-amino acid sensing. J Biol Chem. 2004;279:51739-44 pubmed
    We previously demonstrated that the human calcium-sensing receptor (CaR) is allosterically activated by L-amino acids (Conigrave, A. D., Quinn, S. J., and Brown, E. M. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 4814-4819)...
  2. Vezzoli G, Terranegra A, Arcidiacono T, Gambaro G, Milanesi L, Mosca E, et al. Calcium kidney stones are associated with a haplotype of the calcium-sensing receptor gene regulatory region. Nephrol Dial Transplant. 2010;25:2245-52 pubmed publisher
    ..Calcium-sensing receptor gene (CaSR) is a candidate to explain susceptibility to calcium kidney stones. Thus, we studied CaSR gene single-nucleotide polymorphisms (SNPs) and haplotypes associated with stones...
  3. Falchetti A, Gozzini A, Terranegra A, Soldati L, Vezzoli G, Leoncini G, et al. A novel germline inactivating mutation in the CASR gene in an Italian kindred affected by familial hypocalciuric hypercalcemia. Eur J Endocrinol. 2012;166:933-40 pubmed publisher
    Familial hypocalciuric hypercalcemia (FHH) syndrome is a rare benign condition, inherited as an autosomal dominant trait, in which inactivating mutations of the calcium-sensing receptor (CASR) gene affects the body's ability to regulate ..
  4. Kestenbaum B, Glazer N, Köttgen A, Felix J, Hwang S, Liu Y, et al. Common genetic variants associate with serum phosphorus concentration. J Am Soc Nephrol. 2010;21:1223-32 pubmed publisher
    ..05 for each). In conclusion, common genetic variants associate with serum phosphorus in the general population. Further study of the loci identified in this study may help elucidate mechanisms of phosphorus regulation. ..
  5. Pidasheva S, Grant M, Canaff L, Ercan O, Kumar U, Hendy G. Calcium-sensing receptor dimerizes in the endoplasmic reticulum: biochemical and biophysical characterization of CASR mutants retained intracellularly. Hum Mol Genet. 2006;15:2200-9 pubmed
    ..Hence, constitutive CASR dimerization occurs in the ER and is likely to be necessary, but is not sufficient, for exit of the receptor from the ER and trafficking to the cell surface. ..
  6. Justinich C, Mak N, Pacheco I, Mulder D, Wells R, Blennerhassett M, et al. The extracellular calcium-sensing receptor (CaSR) on human esophagus and evidence of expression of the CaSR on the esophageal epithelial cell line (HET-1A). Am J Physiol Gastrointest Liver Physiol. 2008;294:G120-9 pubmed
    ..We conclude that the CaSR is present on basal cells of the human esophagus and is present in a functional manner on the esophageal epithelial cell line, HET-1A. ..
  7. Speer G, Cseh K, Mucsi K, Takacs I, Dworak O, Winkler G, et al. Calcium-sensing receptor A986S polymorphism in human rectal cancer. Int J Colorectal Dis. 2002;17:20-4 pubmed
    ..During the follow-up period AA genotype showed a tendency for poor prognosis. Our observation raises the possibility that genetic alterations of CaSR influence the pathogenesis of rectal cancer. ..
  8. Hamilton D, Grover V, Smith C, Cole D. Heterogeneous disease modeling for Hardy-Weinberg disequilibrium in case-control studies: application to renal stones and calcium-sensing receptor polymorphisms. Ann Hum Genet. 2009;73:176-83 pubmed publisher
    ..The R990G single-nucleotide polymorphism (SNP) of the calcium sensing receptor (CASR) gene has been associated with hypercalciuria in stone formers and shows the appropriate functional ..
  9. Vezzoli G, Tanini A, Ferrucci L, Soldati L, Bianchin C, Franceschelli F, et al. Influence of calcium-sensing receptor gene on urinary calcium excretion in stone-forming patients. J Am Soc Nephrol. 2002;13:2517-23 pubmed
    ..Arg990Gly polymorphism could facilitate activation of CaSR and increase Ca excretion and susceptibility to idiopathic hypercalciuria. ..
  10. Jacobs E, Martinez M, Campbell P, Conti D, Duggan D, Figueiredo J, et al. Genetic variation in the retinoid X receptor and calcium-sensing receptor and risk of colorectal cancer in the Colon Cancer Family Registry. Carcinogenesis. 2010;31:1412-6 pubmed publisher
    ..29-0.96). These results provide support that RXRA SNPs rs7861779 and rs12004589 and CASR SNP rs1801726 may be important markers for colorectal neoplasia. Further work is needed to elucidate their role in the carcinogenic pathway. ..
  11. Shakhssalim N, Kazemi B, Basiri A, Houshmand M, Pakmanesh H, Golestan B, et al. Association between calcium-sensing receptor gene polymorphisms and recurrent calcium kidney stone disease: a comprehensive gene analysis. Scand J Urol Nephrol. 2010;44:406-12 pubmed publisher
    ..Comprehensive sequencing of the coding exons of the calcium-sensing receptor gene (CASR) was performed in a group of Iranian recurrent calcium kidney stone-formers and the results were compared with a control group...
  12. Kanatani M, Sugimoto T, Kanzawa M, Yano S, Chihara K. High extracellular calcium inhibits osteoclast-like cell formation by directly acting on the calcium-sensing receptor existing in osteoclast precursor cells. Biochem Biophys Res Commun. 1999;261:144-8 pubmed
    ..Furthermore, the CaSR in osteoclast precursor cells could play a key role in regulating Ocl formation by sensing local changes in [Ca(2+)](e) at the resorptive sites. ..
  13. Bai M, Trivedi S, Brown E. Dimerization of the extracellular calcium-sensing receptor (CaR) on the cell surface of CaR-transfected HEK293 cells. J Biol Chem. 1998;273:23605-10 pubmed
    The extracellular calcium (Ca2+o)-sensing receptor (CaR) is a G protein-coupled receptor that plays important roles in calcium homeostasis...
  14. Saidak Z, Mentaverri R, Brown E. The role of the calcium-sensing receptor in the development and progression of cancer. Endocr Rev. 2009;30:178-95 pubmed publisher
    The calcium-sensing receptor (CaR) is responsive to changes in the extracellular Ca(2+) (Ca(2+)(o)) concentration...
  15. Giannini S, Sella S, Silva Netto F, Cattelan C, Dalle Carbonare L, Lazzarin R, et al. Persistent secondary hyperparathyroidism and vertebral fractures in kidney transplantation: role of calcium-sensing receptor polymorphisms and vitamin D deficiency. J Bone Miner Res. 2010;25:841-8 pubmed publisher
    ..High PTH levels, in turn, are associated with an increased VFx risk, which confirms the need for strategies aimed at lowering serum PTH in this setting as well. ..
  16. Rey O, Young S, Jacamo R, Moyer M, Rozengurt E. Extracellular calcium sensing receptor stimulation in human colonic epithelial cells induces intracellular calcium oscillations and proliferation inhibition. J Cell Physiol. 2010;225:73-83 pubmed publisher
    The extracellular Ca(2+)-sensing receptor (CaR) is increasingly implicated in the regulation of multiple cellular functions in the gastrointestinal tract, including secretion, proliferation and differentiation of intestinal epithelial ..
  17. Guarnieri V, Valentina D Elia A, Baorda F, Pazienza V, Benegiamo G, Stanziale P, et al. CASR gene activating mutations in two families with autosomal dominant hypocalcemia. Mol Genet Metab. 2012;107:548-52 pubmed publisher
    ..Our work enlarged the spectrum of mutations of the CASR and contributed to a better elucidation of the protein function. ..
  18. Zhang Z, Qiu W, Quinn S, Conigrave A, Brown E, Bai M. Three adjacent serines in the extracellular domains of the CaR are required for L-amino acid-mediated potentiation of receptor function. J Biol Chem. 2002;277:33727-35 pubmed
    The extracellular calcium (Ca(2+)(o))-sensing receptor (CaR) is a key player in Ca(2+)(o) homeostasis. The activity of CaR can be potentiated by various l-amino acids...
  19. Peters U, Chatterjee N, Yeager M, Chanock S, Schoen R, McGlynn K, et al. Association of genetic variants in the calcium-sensing receptor with risk of colorectal adenoma. Cancer Epidemiol Biomarkers Prev. 2004;13:2181-6 pubmed
    ..However, the power to investigate interactions was limited. Variants in the CASR intracellular signaling region were significantly associated with the risk of advanced adenoma. ..
  20. Silve C, Petrel C, Leroy C, Bruel H, Mallet E, Rognan D, et al. Delineating a Ca2+ binding pocket within the venus flytrap module of the human calcium-sensing receptor. J Biol Chem. 2005;280:37917-23 pubmed
    ..Altogether, these data define a Ca(2+) binding pocket within the CaSR VFTM that may be conserved in several other class III GPCRs, thereby providing a molecular basis for extracellular Ca(2+) sensing by these receptors. ..
  21. Garrett J, Capuano I, Hammerland L, Hung B, Brown E, Hebert S, et al. Molecular cloning and functional expression of human parathyroid calcium receptor cDNAs. J Biol Chem. 1995;270:12919-25 pubmed
    ..This "Ca2+ receptor" (CaR) serves as the primary physiological regulator of parathyroid hormone secretion...
  22. Ziegelstein R, Xiong Y, He C, Hu Q. Expression of a functional extracellular calcium-sensing receptor in human aortic endothelial cells. Biochem Biophys Res Commun. 2006;342:153-63 pubmed
    ..Ca(2+)](o)) regulates the functions of many cell types through a G protein-coupled [Ca(2+)](o)-sensing receptor (CaR). Whether the receptor is functionally expressed in vascular endothelial cells is largely unknown...
  23. Hizaki K, Yamamoto H, Taniguchi H, Adachi Y, Nakazawa M, Tanuma T, et al. Epigenetic inactivation of calcium-sensing receptor in colorectal carcinogenesis. Mod Pathol. 2011;24:876-84 pubmed publisher
    ..CASR methylation seems to occur at an early stage and progress in colorectal carcinogenesis. The results suggest that epigenetic inactivation of CASR has an important role in colorectal carcinogenesis. ..
  24. Hibler E, Hu C, Jurutka P, Martinez M, Jacobs E. Polymorphic variation in the GC and CASR genes and associations with vitamin D metabolite concentration and metachronous colorectal neoplasia. Cancer Epidemiol Biomarkers Prev. 2012;21:368-75 pubmed publisher
    ..Additional research is warranted to determine the mechanism of GC genotype in influencing 25(OH)D concentrations and to further elucidate the role of CASR in colorectal neoplasia. ..
  25. Pollak M, Brown E, Chou Y, Hebert S, Marx S, Steinmann B, et al. Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Cell. 1993;75:1297-303 pubmed
    ..receptor gene cause familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT), two inherited conditions characterized by altered calcium homeostasis...
  26. Hu J, Spiegel A. Structure and function of the human calcium-sensing receptor: insights from natural and engineered mutations and allosteric modulators. J Cell Mol Med. 2007;11:908-22 pubmed
    The human extracellular Ca(2+)-sensing receptor (CaR), a member of the G protein-coupled receptor family 3, plays a key role in the regulation of extracellular calcium homeostasis...
  27. Rothe H, Shapiro W, Sun W, Chou S. Calcium-sensing receptor gene polymorphism Arg990Gly and its possible effect on response to cinacalcet HCl. Pharmacogenet Genomics. 2005;15:29-34 pubmed
  28. Corbetta S, Eller Vainicher C, Filopanti M, Saeli P, Vezzoli G, Arcidiacono T, et al. R990G polymorphism of the calcium-sensing receptor and renal calcium excretion in patients with primary hyperparathyroidism. Eur J Endocrinol. 2006;155:687-92 pubmed
    ..Since this variant was associated with increased occurrence of nephrolithiasis, analysis of this polymorphism might help to predict renal complication of the disease. ..
  29. Guarnieri V, Canaff L, Yun F, Scillitani A, Battista C, Muscarella L, et al. Calcium-sensing receptor (CASR) mutations in hypercalcemic states: studies from a single endocrine clinic over three years. J Clin Endocrinol Metab. 2010;95:1819-29 pubmed publisher
    ..CASR) are implicated in different hypercalcemic syndromes, including familial hypocalciuric hypercalcemia (FHH), primary hyperparathyroidism (PHPT), and familial isolated hyperparathyroidism (FIHP)...
  30. Cole D, Vieth R, Trang H, Wong B, Hendy G, Rubin L. Association between total serum calcium and the A986S polymorphism of the calcium-sensing receptor gene. Mol Genet Metab. 2001;72:168-74 pubmed
    ..The A986S polymorphism is also a potential predisposing factor in disorders of bone and mineral metabolism. ..
  31. Varshney S, Bhadada S, Sachdeva N, Arya A, Saikia U, Behera A, et al. Methylation status of the CpG islands in vitamin D and calcium-sensing receptor gene promoters does not explain the reduced gene expressions in parathyroid adenomas. J Clin Endocrinol Metab. 2013;98:E1631-5 pubmed publisher
    ..We investigated whether epigenetic silencing is involved in the decreased expression of VDR and CASR...
  32. Kelly C, Gunn I, Gaffney D, Devgun M. Serum calcium, urine calcium and polymorphisms of the calcium sensing receptor gene. Ann Clin Biochem. 2006;43:503-6 pubmed
    Recent studies have suggested a correlation between the A986S polymorphism of the calcium sensing receptor (CASR), and serum total and ionized calcium...
  33. Molostvov G, James S, Fletcher S, Bennett J, Lehnert H, Bland R, et al. Extracellular calcium-sensing receptor is functionally expressed in human artery. Am J Physiol Renal Physiol. 2007;293:F946-55 pubmed
    ..Expression was significantly lower in arteries from ESRD patients. In conclusion, these data not only demonstrate the presence of a functional CaSR in human artery but show a correlation between CaSR expression and progression of CKD. ..
  34. Diez Fraile A, Lammens T, Benoit Y, D Herde K. The calcium-sensing receptor as a regulator of cellular fate in normal and pathological conditions. Curr Mol Med. 2013;13:282-95 pubmed
    ..Here, we will review the recent discoveries regarding the relevance of CaSR signaling in development and disease. Furthermore, we will discuss the rational for developing and using CaSR-based therapeutics. ..
  35. Bai M, Quinn S, Trivedi S, Kifor O, Pearce S, Pollak M, et al. Expression and characterization of inactivating and activating mutations in the human Ca2+o-sensing receptor. J Biol Chem. 1996;271:19537-45 pubmed
    Nearly 30 mutations have been identified to date in the coding region of the extracellular calcium-sensing receptor (CaR) that are associated with inherited human hypo- and hypercalcemic disorders...
  36. Hjälm G, MacLeod R, Kifor O, Chattopadhyay N, Brown E. Filamin-A binds to the carboxyl-terminal tail of the calcium-sensing receptor, an interaction that participates in CaR-mediated activation of mitogen-activated protein kinase. J Biol Chem. 2001;276:34880-7 pubmed
    The G protein-coupled, extracellular calcium-sensing receptor (CaR) regulates parathyroid hormone secretion and parathyroid cellular proliferation as well as the functions of diverse other cell types...
  37. Miedlich S, Gama L, Breitwieser G. Calcium sensing receptor activation by a calcimimetic suggests a link between cooperativity and intracellular calcium oscillations. J Biol Chem. 2002;277:49691-9 pubmed
    Activation of the calcium sensing receptor (CaR) by small increments in extracellular calcium (Ca(2+)(e)) induces intracellular calcium (Ca(2+)(i)) oscillations that are dependent on thapsigargin-sensitive intracellular calcium stores...
  38. Scillitani A, Guarnieri V, Battista C, De Geronimo S, Muscarella L, Chiodini I, et al. Primary hyperparathyroidism and the presence of kidney stones are associated with different haplotypes of the calcium-sensing receptor. J Clin Endocrinol Metab. 2007;92:277-83 pubmed
    ..Our data indicate that the CASR SRQ haplotype is significantly associated with PHPT in our population. Within the PHPT patient population, the AGQ haplotype is significantly associated with kidney stones. ..
  39. Vezzoli G, Terranegra A, Arcidiacono T, Biasion R, Coviello D, Syren M, et al. R990G polymorphism of calcium-sensing receptor does produce a gain-of-function and predispose to primary hypercalciuria. Kidney Int. 2007;71:1155-62 pubmed
    ..0001). Our findings indicate that R990G polymorphism results in a gain-of-function of the calcium-sensing receptor and increased susceptibility to primary hypercalciuria. ..
  40. Makita N, Sato J, Manaka K, Shoji Y, Oishi A, Hashimoto M, et al. An acquired hypocalciuric hypercalcemia autoantibody induces allosteric transition among active human Ca-sensing receptor conformations. Proc Natl Acad Sci U S A. 2007;104:5443-8 pubmed
    ..We thus speculate that physiological modulators may exist that enable an agonist to specifically activate only one signaling pathway via a GPCR that activates multiple signaling pathways. ..
  41. März W, Seelhorst U, Wellnitz B, Tiran B, Obermayer Pietsch B, Renner W, et al. Alanine to serine polymorphism at position 986 of the calcium-sensing receptor associated with coronary heart disease, myocardial infarction, all-cause, and cardiovascular mortality. J Clin Endocrinol Metab. 2007;92:2363-9 pubmed
    ..001) and PTH (P < 0.02), and lower phosphate (P < 0.003) in CAD patients and controls. Serine at position 986 of CASR may be an independent genetic predictor of angiographic CAD, previous MI, and cardiovascular mortality. ..
  42. Macleod R, Hayes M, Pacheco I. Wnt5a secretion stimulated by the extracellular calcium-sensing receptor inhibits defective Wnt signaling in colon cancer cells. Am J Physiol Gastrointest Liver Physiol. 2007;293:G403-11 pubmed
    ..Our findings demonstrate that APC status plays a key role as a determinant of Wnt5a secretion and suggest that CaSR-mediated secretion of Wnt5a will inhibit defective Wnt signaling in APC-truncated cells in an autocrine manner. ..
  43. Alam M, Kirton J, Wilkinson F, Towers E, Sinha S, Rouhi M, et al. Calcification is associated with loss of functional calcium-sensing receptor in vascular smooth muscle cells. Cardiovasc Res. 2009;81:260-8 pubmed publisher
    ..Allosteric modulation of the calcium-sensing receptor (CaR) by calcimimetics inhibits VC in animal models of advanced CKD...
  44. Bacsi K, Hitre E, Kósa J, Horváth H, Lazary A, Lakatos P, et al. Effects of the lactase 13910 C/T and calcium-sensor receptor A986S G/T gene polymorphisms on the incidence and recurrence of colorectal cancer in Hungarian population. BMC Cancer. 2008;8:317 pubmed publisher
    ..035). The CCSS genotype combination was found only in patients with CRC (p = 0.033). LCT 13910 C/T and CaSR A986S polymorphisms may have an impact on the progression and/or incidence of CRC. ..
  45. Nakajima K, Yamazaki K, Kimura H, Takano K, Miyoshi H, Sato K. Novel gain of function mutations of the calcium-sensing receptor in two patients with PTH-deficient hypocalcemia. Intern Med. 2009;48:1951-6 pubmed
    ..These findings suggest that gene analysis of CaSR should be performed in patients with idiopathic hypocalcemia, particularly when it occurs in the neonatal period. ..
  46. Procino G, Mastrofrancesco L, Tamma G, Lasorsa D, Ranieri M, Stringini G, et al. Calcium-sensing receptor and aquaporin 2 interplay in hypercalciuria-associated renal concentrating defect in humans. An in vivo and in vitro study. PLoS ONE. 2012;7:e33145 pubmed publisher
    One mechanism proposed for reducing the risk of calcium renal stones is activation of the calcium-sensing receptor (CaR) on the apical membranes of collecting duct principal cells by high luminal calcium...
  47. Hannan F, Nesbit M, Zhang C, Cranston T, Curley A, Harding B, et al. Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites. Hum Mol Genet. 2012;21:2768-78 pubmed publisher
    ..unrelated probands with familial hypocalciuric hypercalcaemia (FHH), neonatal severe primary hyperparathyroidism (NSHPT) or autosomal dominant hypocalcaemic hypercalciuria (ADHH) for CaSR mutations and performed in vitro functional ..
  48. Bai M, Trivedi S, Lane C, Yang Y, Quinn S, Brown E. Protein kinase C phosphorylation of threonine at position 888 in Ca2+o-sensing receptor (CaR) inhibits coupling to Ca2+ store release. J Biol Chem. 1998;273:21267-75 pubmed
    Previous studies in parathyroid cells, which express the G protein-coupled, extracellular calcium-sensing receptor (CaR), showed that activation of protein kinase C (PKC) blunts high extracellular calcium (Ca2+o)-evoked stimulation of ..
  49. Lorentzon M, Lorentzon R, Lerner U, Nordstrom P. Calcium sensing receptor gene polymorphism, circulating calcium concentrations and bone mineral density in healthy adolescent girls. Eur J Endocrinol. 2001;144:257-61 pubmed
    Bone mineral density (BMD) in adolescence is under strong genetic control. The calcium sensing receptor (CASR) is involved in the regulation of calcium homeostasis and bone resorption...
  50. Scillitani A, Guarnieri V, De Geronimo S, Muscarella L, Battista C, D Agruma L, et al. Blood ionized calcium is associated with clustered polymorphisms in the carboxyl-terminal tail of the calcium-sensing receptor. J Clin Endocrinol Metab. 2004;89:5634-8 pubmed
    ..Given the significant between-population variations in frequency of variant alleles in this CASR SNP cluster, tri-locus haplotyping may prove to be more informative in studies of association between variation in CASR and disease. ..
  51. Bhagavathula N, Kelley E, Reddy M, Nerusu K, Leonard C, Fay K, et al. Upregulation of calcium-sensing receptor and mitogen-activated protein kinase signalling in the regulation of growth and differentiation in colon carcinoma. Br J Cancer. 2005;93:1364-71 pubmed
    ..They appear to function, at least in part, independently of one another. ..
  52. Huang Y, Breitwieser G. Rescue of calcium-sensing receptor mutants by allosteric modulators reveals a conformational checkpoint in receptor biogenesis. J Biol Chem. 2007;282:9517-25 pubmed
    The calcium-sensing receptor (CaR), a member of G protein-coupled receptor family C, regulates systemic calcium homeostasis by activating G(q)- and G(i)-linked signaling in the parathyroid, kidney, and intestine...
  53. Mamillapalli R, VanHouten J, Zawalich W, Wysolmerski J. Switching of G-protein usage by the calcium-sensing receptor reverses its effect on parathyroid hormone-related protein secretion in normal versus malignant breast cells. J Biol Chem. 2008;283:24435-47 pubmed publisher
    The calcium-sensing receptor (CaR) is a G-protein-coupled receptor that signals in response to extracellular calcium and regulates parathyroid hormone secretion...
  54. de Torres C, Beleta H, Diaz R, Toran N, Rodriguez E, Lavarino C, et al. The calcium-sensing receptor and parathyroid hormone-related protein are expressed in differentiated, favorable neuroblastic tumors. Cancer. 2009;115:2792-803 pubmed publisher
    ..The calcium-sensing receptor (CaR) and parathyroid hormone-related protein (PTHrP) regulate differentiation processes in some cellular contexts...
  55. Raue F, Pichl J, Dörr H, Schnabel D, Heidemann P, Hammersen G, et al. Activating mutations in the calcium-sensing receptor: genetic and clinical spectrum in 25 patients with autosomal dominant hypocalcaemia - a German survey. Clin Endocrinol (Oxf). 2011;75:760-5 pubmed publisher
    ..Mutation analysis of the CaSR gene facilitates patient and family management. Low dosages of calcitriol resulted in less frequent renal calcifications. ..
  56. Rey O, Chang W, Bikle D, Rozengurt N, Young S, Rozengurt E. Negative cross-talk between calcium-sensing receptor and ?-catenin signaling systems in colonic epithelium. J Biol Chem. 2012;287:1158-67 pubmed publisher
    ..These studies demonstrate that signaling pathways emanating from the CaSR control colonic epithelial cell proliferation in vivo and suggest that the mechanism involves regulation of ?-catenin phosphorylation. ..
  57. Park S, Mun H, Eom Y, Baek H, Jung T, Kim C, et al. Identification and characterization of D410E, a novel mutation in the loop 3 domain of CASR, in autosomal dominant hypocalcemia and a therapeutic approach using a novel calcilytic, AXT914. Clin Endocrinol (Oxf). 2013;78:687-93 pubmed publisher
    ..Further clinical study will be needed to validate the effectiveness of calcilytics in treatment of ADH in vivo. ..
  58. Malecki R, Fiodorenko Dumas Ż, Jakobsche Policht U, Malodobra M, Adamiec R. Altered monocyte calcium-sensing receptor expression in patients with type 2 diabetes mellitus and atherosclerosis. J Physiol Pharmacol. 2013;64:521-7 pubmed
    ..The aim of this study was to analyze the expression of calcium-sensing receptor (CaR) in peripheral blood monocytes of individuals with DM2 and peripheral artery disease (PAD)...
  59. Pollak M, Brown E, Estep H, McLaine P, Kifor O, Park J, et al. Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation. Nat Genet. 1994;8:303-7 pubmed
    ..We conclude that this extracellular domain mutation increases the receptor's activity at low Ca2+ concentrations, causing hypocalcaemia in patients heterozygous for such a mutation. ..
  60. Hendy G, D Souza Li L, Yang B, Canaff L, Cole D. Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia. Hum Mutat. 2000;16:281-96 pubmed
    ..The homozygous condition manifests itself as neonatal severe hyperparathyroidism (NSHPT), a rare disorder characterized by extreme hypercalcemia and the bony changes of hyperparathyroidism which occur ..
  61. Yamauchi M, Sugimoto T, Yamaguchi T, Yano S, Kanzawa M, Kobayashi A, et al. Association of polymorphic alleles of the calcium-sensing receptor gene with the clinical severity of primary hyperparathyroidism. Clin Endocrinol (Oxf). 2001;55:373-9 pubmed
    ..The Ca-sensing receptor (CaR) is activated by an extracellular calcium ion and controls PTH secretion, and thus polymorphisms of CaR might be ..
  62. Canaff L, Hendy G. Calcium-sensing receptor gene transcription is up-regulated by the proinflammatory cytokine, interleukin-1beta. Role of the NF-kappaB PATHWAY and kappaB elements. J Biol Chem. 2005;280:14177-88 pubmed
    ..In summary, the CASR gene has several functional kappaB elements that mediate its upregulation by proinflammatory cytokines and probably contribute to altered extracellular calcium homeostasis in the critically ill. ..
  63. Harding B, Curley A, Hannan F, Christie P, Bowl M, Turner J, et al. Functional characterization of calcium sensing receptor polymorphisms and absence of association with indices of calcium homeostasis and bone mineral density. Clin Endocrinol (Oxf). 2006;65:598-605 pubmed
  64. Yun F, Wong B, Chase M, Shuen A, Canaff L, Thongthai K, et al. Genetic variation at the calcium-sensing receptor (CASR) locus: implications for clinical molecular diagnostics. Clin Biochem. 2007;40:551-61 pubmed
    ..They will assist in the study of CASR polymorphisms as predictors of complex disease states. ..
  65. Huang Y, Zhou Y, Yang W, Butters R, Lee H, Li S, et al. Identification and dissection of Ca(2+)-binding sites in the extracellular domain of Ca(2+)-sensing receptor. J Biol Chem. 2007;282:19000-10 pubmed [Ca(2+)](o), similar to those observed with naturally occurring activating or inactivating mutations of the CaR, supporting the essential role of these predicted Ca(2+)-binding sites in the sensing capability of the CaSR...
  66. Cifuentes M, Rojas C. Antilipolytic effect of calcium-sensing receptor in human adipocytes. Mol Cell Biochem. 2008;319:17-21 pubmed publisher
  67. Pacheco I, Macleod R. CaSR stimulates secretion of Wnt5a from colonic myofibroblasts to stimulate CDX2 and sucrase-isomaltase using Ror2 on intestinal epithelia. Am J Physiol Gastrointest Liver Physiol. 2008;295:G748-59 pubmed publisher
  68. Jenab M, McKay J, Bueno de Mesquita H, van Duijnhoven F, Ferrari P, Slimani N, et al. Vitamin D receptor and calcium sensing receptor polymorphisms and the risk of colorectal cancer in European populations. Cancer Epidemiol Biomarkers Prev. 2009;18:2485-91 pubmed publisher
    ..suggested that these effects may be mediated by genetic variants of the vitamin D receptor (VDR) and the calcium sensing receptor (CASR)...
  69. Ray K, Clapp P, Goldsmith P, Spiegel A. Identification of the sites of N-linked glycosylation on the human calcium receptor and assessment of their role in cell surface expression and signal transduction. J Biol Chem. 1998;273:34558-67 pubmed
  70. Jiang Y, Zhang Z, Kifor O, Lane C, Quinn S, Bai M. Protein kinase C (PKC) phosphorylation of the Ca2+ o-sensing receptor (CaR) modulates functional interaction of G proteins with the CaR cytoplasmic tail. J Biol Chem. 2002;277:50543-9 pubmed
    The extracellular calcium (Ca(2+)(o))-sensing receptor (CaR) activates Ca(2+) influx independent of the release of intracellular Ca(2+) stores...
  71. Chakrabarty S, Radjendirane V, Appelman H, Varani J. Extracellular calcium and calcium sensing receptor function in human colon carcinomas: promotion of E-cadherin expression and suppression of beta-catenin/TCF activation. Cancer Res. 2003;63:67-71 pubmed
    ..different human colon carcinoma cell lines (FET, SW480, MOSER, and CBS) expressed the human parathyroid calcium sensing receptor (CaSR) and that a function of extracellular Ca(2+) and the CaSR in these cells was the promotion of E-..
  72. Hu J, Spiegel A. Naturally occurring mutations of the extracellular Ca2+-sensing receptor: implications for its structure and function. Trends Endocrinol Metab. 2003;14:282-8 pubmed
  73. Bollerslev J, Wilson S, Dick I, Devine A, Dhaliwal S, Prince R. Calcium-sensing receptor gene polymorphism A986S does not predict serum calcium level, bone mineral density, calcaneal ultrasound indices, or fracture rate in a large cohort of elderly women. Calcif Tissue Int. 2004;74:12-7 pubmed
    ..It is questioned whether the polymorphism has any clinical significance for postmenopausal osteoporosis. ..
  74. Goswami R, Brown E, Kochupillai N, Gupta N, Rani R, Kifor O, et al. Prevalence of calcium sensing receptor autoantibodies in patients with sporadic idiopathic hypoparathyroidism. Eur J Endocrinol. 2004;150:9-18 pubmed
    The pathogenesis of sporadic idiopathic hypoparathyroidism is unclear. The calcium sensing receptor (CaSR) plays a pivotal role in extracellular calcium homeostasis and is the candidate autoantigen in hypoparathyroidism associated with ..
  75. Pidasheva S, Canaff L, Simonds W, Marx S, Hendy G. Impaired cotranslational processing of the calcium-sensing receptor due to signal peptide missense mutations in familial hypocalciuric hypercalcemia. Hum Mol Genet. 2005;14:1679-90 pubmed
    ..The inherited disorders, familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT), are caused by inactivating mutations in the CASR gene...
  76. Peiris D, Pacheco I, Spencer C, Macleod R. The extracellular calcium-sensing receptor reciprocally regulates the secretion of BMP-2 and the BMP antagonist Noggin in colonic myofibroblasts. Am J Physiol Gastrointest Liver Physiol. 2007;292:G753-66 pubmed
    ..Together, our data suggest that the CaSR mediates the effective concentration of BMP-2 in the intestine, which leads to enhanced repair and barrier development. ..
  77. Egbuna O, Brown E. Hypercalcaemic and hypocalcaemic conditions due to calcium-sensing receptor mutations. Best Pract Res Clin Rheumatol. 2008;22:129-48 pubmed publisher
    ..Calcimimetic CaSR activators and calcilytic CaSR antagonists have also been developed with potential for use in the treatment of these disorders. ..
  78. Ferreira L, Pereira A, Heilberg I. Vitamin D receptor and calcium-sensing receptor gene polymorphisms in hypercalciuric stone-forming patients. Nephron Clin Pract. 2010;114:c135-44 pubmed publisher
    ..The present study suggested that bb homozygous for VDR polymorphism was overrepresented in hypercalciuric stone formers. Urinary calcium excretion was not associated with CaSR polymorphism in the present sample. ..
  79. Vezzoli G, Scillitani A, Corbetta S, Terranegra A, Dogliotti E, Guarnieri V, et al. Polymorphisms at the regulatory regions of the CASR gene influence stone risk in primary hyperparathyroidism. Eur J Endocrinol. 2011;164:421-7 pubmed publisher
    ..To confirm their association with nephrolithiasis, we tested patients with primary hyperparathyroidism (PHPT)...
  80. Heath H, Odelberg S, Jackson C, Teh B, Hayward N, Larsson C, et al. Clustered inactivating mutations and benign polymorphisms of the calcium receptor gene in familial benign hypocalciuric hypercalcemia suggest receptor functional domains. J Clin Endocrinol Metab. 1996;81:1312-7 pubmed
    ..FBHH) is FBHH(3q), which is associated with presumed inactivating mutations of the cell surface calcium receptor (CaR) gene on chromosome 3q13.3-q21...
  81. Cetani F, Borsari S, Vignali E, Pardi E, Picone A, Cianferotti L, et al. Calcium-sensing receptor gene polymorphisms in primary hyperparathyroidism. J Endocrinol Invest. 2002;25:614-9 pubmed
    The calcium-sensing receptor (CaR) polymorphism A986S has been found to be associated with higher serum calcium levels in normal subjects, suggesting that this amino acid change might decrease the inhibitory activity of the mutated ..
  82. Huang Y, Niwa J, Sobue G, Breitwieser G. Calcium-sensing receptor ubiquitination and degradation mediated by the E3 ubiquitin ligase dorfin. J Biol Chem. 2006;281:11610-7 pubmed
    Calcium-sensing receptors (CaR) contribute to regulation of systemic calcium homeostasis by activation of G(q)- and G(i)-linked signaling pathways in the parathyroids, kidney, and intestine...
  83. Gavalas N, Kemp E, Krohn K, Brown E, Watson P, Weetman A. The calcium-sensing receptor is a target of autoantibodies in patients with autoimmune polyendocrine syndrome type 1. J Clin Endocrinol Metab. 2007;92:2107-14 pubmed
    ..023). No CaSR antibodies could be detected in any patients or controls using a radiobinding assay. The CaSR is an autoantigen in APS1, but detection of antibodies against the receptor appears to be influenced by the assay system used. ..
  84. Canaff L, Zhou X, Hendy G. The proinflammatory cytokine, interleukin-6, up-regulates calcium-sensing receptor gene transcription via Stat1/3 and Sp1/3. J Biol Chem. 2008;283:13586-600 pubmed publisher
    ..In conclusion, Stat1/3 directly controls promoter P1, and the Stats indirectly regulate promoter P2 via Sp1/3 in response to IL-6. By this mechanism, the cytokine likely contributes to altered extracellular calcium homeostasis. ..
  85. Liu G, Hu X, Chakrabarty S. Vitamin D mediates its action in human colon carcinoma cells in a calcium-sensing receptor-dependent manner: downregulates malignant cell behavior and the expression of thymidylate synthase and survivin and promotes cellular sensitivity to 5-FU. Int J Cancer. 2010;126:631-9 pubmed publisher
    ..VD, however, could no longer enhance cellular sensitivity to 5-FU in cells overexpressing CaSR. ..
  86. Dong Q, Cheng Z, Chang W, Blackman B, Conte F, Hu J, et al. Naturally-occurring mutation in the calcium-sensing receptor reveals the significance of extracellular domain loop III region for class C G-protein-coupled receptor function. J Clin Endocrinol Metab. 2010;95:E245-52 pubmed publisher
    ..Absence of conserved Asn345 may interfere with CaSR folding or glycosylation, leading to poor protein targeting to the cell membrane. This loss-of-function mutant indicates that the ECD loop III is required for CaSR activity. ..
  87. Letz S, Rus R, Haag C, Dörr H, Schnabel D, Mohlig M, et al. Novel activating mutations of the calcium-sensing receptor: the calcilytic NPS-2143 mitigates excessive signal transduction of mutant receptors. J Clin Endocrinol Metab. 2010;95:E229-33 pubmed publisher
    ..The mutant P221L, however, was only responsive when coexpressed with the wild-type CaSR. Calcilytics might offer medical treatment for patients with autosomal dominant hypocalcemia caused by calcilytic-sensitive CaSR mutants. ..
  88. O Seaghdha C, Yang Q, Glazer N, Leak T, Dehghan A, Smith A, et al. Common variants in the calcium-sensing receptor gene are associated with total serum calcium levels. Hum Mol Genet. 2010;19:4296-303 pubmed publisher
    ..We conclude that common genetic variation in the CASR gene is associated with similar but milder features in the general population. ..
  89. Ranjzad F, Mahban A, Shemirani A, Mahmoudi T, Vahedi M, Nikzamir A, et al. Influence of gene variants related to calcium homeostasis on biochemical parameters of women with polycystic ovary syndrome. J Assist Reprod Genet. 2011;28:225-32 pubmed publisher
    ..evaluate the associations between polymorphisms in vitamin D receptor (VDR), parathyroid hormone (PTH), calcium sensing receptor (CASR), insulin receptor (INSR), and adiponectin (ADIPOQ) genes and biochemical characteristics of women ..
  90. Pearce S, Bai M, Quinn S, Kifor O, Brown E, Thakker R. Functional characterization of calcium-sensing receptor mutations expressed in human embryonic kidney cells. J Clin Invest. 1996;98:1860-6 pubmed
    ..have been described in the disorders familial benign hypercalcemia (FBH), neonatal severe hyperparathyroidism (NSHPT), and autosomal dominant hypocalcaemia (ADH), and studied their function by characterizing intracellular calcium [..
  91. El Hiani Y, Ahidouch A, Lehen kyi V, Hague F, Gouilleux F, Mentaverri R, et al. Extracellular signal-regulated kinases 1 and 2 and TRPC1 channels are required for calcium-sensing receptor-stimulated MCF-7 breast cancer cell proliferation. Cell Physiol Biochem. 2009;23:335-46 pubmed publisher
    The calcium-sensing receptor (CaR), is a G protein-dependent receptor that responds to increments in extracellular Ca(2+) ([Ca(2+)](o))...
  92. Hannan F, Nesbit M, Christie P, Lissens W, Van Der Schueren B, Bex M, et al. A homozygous inactivating calcium-sensing receptor mutation, Pro339Thr, is associated with isolated primary hyperparathyroidism: correlation between location of mutations and severity of hypercalcaemia. Clin Endocrinol (Oxf). 2010;73:715-22 pubmed publisher
    ..A CaSR missense mutation causing a loss-of-receptor-function can cause symptomatic primary hyperparathyroidism in adulthood. ..