Parathyroid hormone receptors: Introduction


Parathyroid hormone (PTH), parathyroid hormone-related protein (PTHrP), and tuberoinfundibular peptide of thirty-nine residues (TIP39) are endogenous ligands for the parathyroid hormone type 1 and 2 parathyroid hormone receptors. PTH is a classic endocrine hormone essential for mineral homeostasis [43]. It is synthesized as a pre-pro-protein by chief cells of the parathyroid gland. Its secretion is regulated by plasma calcium levels via a calcium-sensing receptor, a G protein-coupled receptor (GPCR). Mature PTH is an 84 residue polypeptide. Most of the characterized effects of PTH can be brought about by the first 34 N-terminal residues of this polypeptide, and PTH(1-34) that is the most commonly used receptor ligand.

PTHrP is the product of a distinct gene [18,41,49]. It has about 70% sequence identity with PTH over the first 34 N-terminal residues that interact with the receptor transmembrane domains and extracellular loops. The effects of exogenous PTHrP are indistinguishable from those of PTH. PTHrP was originally identified as humoral hypercalcemia of malignancy factor, an activity secreted by a number of different tumors. It is now known to be a widely distributed paracrine factor, and has been shown to play a role in the development and remodeling of many tissues, in transepithelial calcium transport, and in smooth muscle relaxation.

TIP39 shares four amino acid identities with both PTH and PTHrP, and six with PTH [54]. Many more of its residues share similar charge or hydrophobicity and it has a similar conformation [42]. It was purified from bovine hypothalamus on the basis of its activation of the parathyroid hormone 2 (PTH2) receptor ([53]; see below). Its physiological role(s) remain to be established. Some evidence supports its involvement in regulation of nociception, hypothalamic, and anxiety-related functions [11,51].


A common receptor for PTH and PTHrP is referred to as the PTH/PTHrP or PTH1 receptor. It was originally cloned from opossum kidney [30] and bone tumor cell lines [1]. It is a member of Family B GPCRs. PTH and PTHrP have virtually indistinguishable interactions with the cloned PTH1 receptor, when using traditional bioassays performed under equilibrium conditions, including high affinity binding and stimulation of cAMP and cytoplasmic calcium accumulation in cells transfected with the receptor [16]. Evidence supports coupling to both Gs and Gq G-proteins [39]. PTH1 receptor signaling via Gs or Gq is regulated in a cell- and ligand-specific manner by β-arrestins [20,57,60]] and the PDZ protein NHERF1 [33,59]. PTH1 receptor expression is particularly high in skeletal tissues and kidney but it has a nearly ubiquitous tissue distribution.

The PTH2 receptor was identified in a sequence based screen for novel Family B GPCRs present in brain-derived cDNA libraries [52]. It has about 50% sequence identity with the PTH1 receptor. It is most abundant in brain and testes, and low levels have been reported in a number of other tissues [50]. The human PTH2 receptor is potently activated by PTH. Failure by one group of investigators to detect PTH synthesis in the brain, and poor activation of the rat PTH2 receptor by PTH, lead to the discovery of TIP39 [53]. TIP39 is a high affinity, potent agonist at both the human and rat PTH2 receptors. It has low affinity and negligible agonism at PTH1 receptors. An excellent match between the neuroanatomical distributions of TIP39 and the PTH2 receptor supports the identification of TIP39 as the endogenous ligand of the PTH2 receptor [10].

Additional receptors for PTHrP, PTH and specific fragments of these proteins have been proposed by a number of investigators based on effects that do not appear to be explained by the currently known receptors [37], but so far no other additional molecularly distinct receptors have been identified in mammals.

There is an extensive body of work aimed at defining the functions of particular domains and residues within the PTH1 receptor, reviewed in [18,58]. A PTH1 receptor isoform lacking the 7th transmembrane domain and that acts as a dominant-negative to suppress wild-type receptor trafficking has been identified and may account for some forms of PTH resistance [2]. Some of this work takes advantage of the partially overlapping ligand selectivity of the PTH1 and PTH2 receptors to define features that contribute to their specificity.

Receptor-ligand interaction

Most pharmacological investigation of PTH receptors uses modified endogenous peptide ligands. Peptides containing the first 34 N-terminal residues of PTH or first 36 of PTHrP are commonly used, and several substitutions have been introduced to increase the peptides stability or to facilitate radioiodination. Residues within the amino terminus of PTH and PTHrP contribute relatively little to the affinity of receptor binding but are essential for receptor activation [46]. Amino-terminal PTH fragment analogs containing affinity-enhancing substitutions in the N-terminal region exhibit high potency on the PTH1 receptor [40,47-48]. PTH/PTHrP hybrids and conformationally constrained cyclic PTH and PTHrP analogs were critical in understanding SAR and bioactive conformation [3-4,34,36]. Peptides lacking several of the amino terminal residues are used as antagonists [12,38]. Removing amino terminal residues from TIP39 decreased its potency as a PTH2 receptor agonist, but deleting enough residues to remove all detectable agonism greatly reduced its affinity for the PTH2 receptor [21]. In contrast, removing amino terminal residues increased the affinity of TIP39 for the PTH1 receptor, and a TIP39 analog lacking amino terminal residues is a potent PTH1 receptor antagonist [26]. A TIP39 analog with four amino acid substitutions near the N-terminal is a PTH2 receptor antagonist with very low affinity for the PTH1 receptor [32].

Only a few small molecule ligands have been reported for the PTH1 receptor, and most of these are low affinity antagonists, although some antagonists have been developed with near-nanomolar affinities [35]. The compound SW106 is a micromolar antagonist that competitively inhibits the binding of a modified M-PTH(1-14) analog, and thus binds to the transmembrane domain/extracellular loop region of the receptor [5]. Compound AH-3960 is the only small molecule compound that exhibits agonist activity on the PTH1 receptor, albeit potency is in the low micromolar range [35].

Almost all studies of ligand binding to PTH receptors have been performed with intact cells. One set of studies has described use of membrane preparations and evaluation of different G-protein interacting states [22-25,27]. Amino-terminally modified PTH(1-34) and PTH(1-28) analogs that exhibit high affinity for the PTHR1 even in the presence of GTPγS, are thought to bind to a novel G protein-independent conformation, called R0 [8,40]. The stable binding of these analogs to the receptor is paralleled by prolonged cAMP signaling responses in cells, and prolonged calcemic and phosphaturic responses in mice [14-15,40]. Förster resonance energy transfer (FRET)-based approaches have been used to measure in real time in live cells kinetics of biochemical reactions involved in the signaling cascade of PTHR. These kinetics revealed ligand–receptor interaction mechanisms and rate-limiting reactions engaged in activation of PTHR and its cognate GS protein [6,15].

A new mechanism of signal transduction for the PTH1R

It has been generally assumed that the production of cAMP mediated by GPCR and termination of signaling take place exclusively at the plasma membrane. Recent studies reveal that the PTH1 receptor does not always follow this conventional paradigm. In the new model, PTH and high-affinity conformation (R0) selective PTH analogs trigger cAMP production not only from the plasma membrane, but also from endosomal membranes [15,55]. This new model proposes that internalization of cell surface ligand-PTH1 receptor complexes into early endosomes maintains cAMP production for an extended period of time. This model is now widely appreciated to be a new component to GPCR signal transduction [56]. Parts of the molecular and cellular mechanisms of this unexpected process have been determined in the case of the PTH1 receptor [14,17,19,60] but the physiological consequences of this model for human biology remain undetermined.

Disease association

Because of its critical role in regulation of calcium metabolism and bone growth and remodeling the PTH1 receptor is of great interest in the treatment of osteoporosis [44]. This PTH1 receptor is also relevant to hypoparathyroidism, and several genetic diseases have been demonstrated to result from its mutants. Blomstrand's lethal chondrodysplasia results from inactivating mutations in the PTH1 receptor [29,31]. Mutations in the PTH1 receptor that lead to increased constituitive activity cause Jansen's metaphyseal chondrodysplasia [45], a disease in which abnormal growth plate organization leads to short stature via shortening of the long bones. Furthermore, PTH1 receptor mutations have been found in patients with Eiken’s disease [13], in some patients with Ollier’s disease [7,28], and in patients with autosomal dominant, isolated primary failure of tooth eruption [9,61].


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1. Abou-Samra AB, Jüppner H, Force T, Freeman MW, Kong XF, Schipani E, Urena P, Richards J, Bonventre JV, Potts Jr JT et al.. (1992) Expression cloning of a common receptor for parathyroid hormone and parathyroid hormone-related peptide from rat osteoblast-like cells: a single receptor stimulates intracellular accumulation of both cAMP and inositol trisphosphates and increases intracellular free calcium. Proc Natl Acad Sci USA, 89 (7): 2732-6. [PMID:1313566]

2. Alonso V, Ardura JA, Wang B, Sneddon WB, Friedman PA. (2011) A naturally occurring isoform inhibits parathyroid hormone receptor trafficking and signaling. J Bone Miner Res, 26 (1): 143-55. [PMID:20578167]

3. Behar V, Nakamoto C, Greenberg Z, Bisello A, Suva LJ, Rosenblatt M, Chorev M. (1996) Histidine at position 5 is the specificity "switch" between two parathyroid hormone receptor subtypes. Endocrinology, 137 (10): 4217-24. [PMID:8828480]

4. Bisello A, Nakamoto C, Rosenblatt M, Chorev M. (1997) Mono- and bicyclic analogs of parathyroid hormone-related protein. 1. Synthesis and biological studies. Biochemistry, 36 (11): 3293-9. [PMID:9116007]

5. Carter PH, Liu RQ, Foster WR, Tamasi JA, Tebben AJ, Favata M, Staal A, Cvijic ME, French MH, Dell V et al.. (2007) Discovery of a small molecule antagonist of the parathyroid hormone receptor by using an N-terminal parathyroid hormone peptide probe. Proc Natl Acad Sci USA, 104 (16): 6846-51. [PMID:17428923]

6. Castro M, Nikolaev VO, Palm D, Lohse MJ, Vilardaga JP. (2005) Turn-on switch in parathyroid hormone receptor by a two-step parathyroid hormone binding mechanism. Proc Natl Acad Sci USA, 102 (44): 16084-9. [PMID:16236727]

7. Couvineau A, Wouters V, Bertrand G, Rouyer C, Gérard B, Boon LM, Grandchamp B, Vikkula M, Silve C. (2008) PTHR1 mutations associated with Ollier disease result in receptor loss of function. Hum Mol Genet, 17 (18): 2766-75. [PMID:18559376]

8. Dean T, Linglart A, Mahon MJ, Bastepe M, Jüppner H, Potts JT, Gardella TJ. (2006) Mechanisms of ligand binding to the parathyroid hormone (PTH)/PTH-related protein receptor: selectivity of a modified PTH(1-15) radioligand for GalphaS-coupled receptor conformations. Mol Endocrinol, 20 (4): 931-43. [PMID:16339275]

9. Decker E, Stellzig-Eisenhauer A, Fiebig BS, Rau C, Kress W, Saar K, Rüschendorf F, Hubner N, Grimm T, Weber BH. (2008) PTHR1 loss-of-function mutations in familial, nonsyndromic primary failure of tooth eruption. Am J Hum Genet, 83 (6): 781-6. [PMID:19061984]

10. Dobolyi A, Irwin S, Wang J, Usdin TB. (2006) The distribution and neurochemistry of the parathyroid hormone 2 receptor in the rat hypothalamus. Neurochem Res, 31 (2): 227-36. [PMID:16570212]

11. Dobolyi A, Palkovits M, Usdin TB. (2010) The TIP39-PTH2 receptor system: unique peptidergic cell groups in the brainstem and their interactions with central regulatory mechanisms. Prog Neurobiol, 90 (1): 29-59. [PMID:19857544]

12. Dresner-Pollak R, Yang QM, Behar V, Nakamoto C, Chorev M, Rosenblatt M. (1996) Evaluation in vivo of a potent parathyroid hormone antagonist: [Nle8,18,D-Trp12,Tyr34]bPTH(7-34)NH2. J Bone Miner Res, 11 (8): 1061-5. [PMID:8854241]

13. Duchatelet S, Ostergaard E, Cortes D, Lemainque A, Julier C. (2005) Recessive mutations in PTHR1 cause contrasting skeletal dysplasias in Eiken and Blomstrand syndromes. Hum Mol Genet, 14 (1): 1-5. [PMID:15525660]

14. Feinstein TN, Wehbi VL, Ardura JA, Wheeler DS, Ferrandon S, Gardella TJ, Vilardaga JP. (2011) Retromer terminates the generation of cAMP by internalized PTH receptors. Nat Chem Biol, 7 (5): 278-84. [PMID:21445058]

15. Ferrandon S, Feinstein TN, Castro M, Wang B, Bouley R, Potts JT, Gardella TJ, Vilardaga JP. (2009) Sustained cyclic AMP production by parathyroid hormone receptor endocytosis. Nat Chem Biol, 5 (10): 734-42. [PMID:19701185]

16. Gardella TJ, Jüppner H. (2001) Molecular properties of the PTH/PTHrP receptor. Trends Endocrinol Metab, 12 (5): 210-7. [PMID:11397646]

17. Gardella TJ, Vilardaga JP. (2015) International Union of Basic and Clinical Pharmacology. XCIII. The Parathyroid Hormone Receptors-Family B G Protein-Coupled Receptors. Pharmacol Rev, 67 (2): 310-37. [PMID:25713287]

18. Gensure RC, Gardella TJ, Jüppner H. (2005) Parathyroid hormone and parathyroid hormone-related peptide, and their receptors. Biochem Biophys Res Commun, 328 (3): 666-78. [PMID:15694400]

19. Gidon A, Al-Bataineh MM, Jean-Alphonse FG, Stevenson HP, Watanabe T, Louet C, Khatri A, Calero G, Pastor-Soler NM, Gardella TJ et al.. (2014) Endosomal GPCR signaling turned off by negative feedback actions of PKA and v-ATPase. Nat Chem Biol, 10 (9): 707-9. [PMID:25064832]

20. Heise GA, Hrabrich B, Lilie NL, Martin RA. (1975) Scopolamine effects on delayed spatial alternation in the rat. Pharmacol Biochem Behav, 3 (6): 993-1002. [PMID:1223909]

21. Hoare SR, Clark JA, Usdin TB. (2000) Molecular determinants of tuberoinfundibular peptide of 39 residues (TIP39) selectivity for the parathyroid hormone-2 (PTH2) receptor. N-terminal truncation of TIP39 reverses PTH2 receptor/PTH1 receptor binding selectivity. J Biol Chem, 275 (35): 27274-83. [PMID:10854439]

22. Hoare SR, de Vries G, Usdin TB. (1999) Measurement of agonist and antagonist ligand-binding parameters at the human parathyroid hormone type 1 receptor: evaluation of receptor states and modulation by guanine nucleotide. J Pharmacol Exp Ther, 289 (3): 1323-33. [PMID:10336523]

23. Hoare SR, Gardella TJ, Usdin TB. (2001) Evaluating the signal transduction mechanism of the parathyroid hormone 1 receptor. Effect of receptor-G-protein interaction on the ligand binding mechanism and receptor conformation. J Biol Chem, 276 (11): 7741-53. [PMID:11108715]

24. Hoare SR, Usdin TB. (1999) Quantitative cell membrane-based radioligand binding assays for parathyroid hormone receptors. J Pharmacol Toxicol Methods, 41: 83-90. [PMID:10598679]

25. Hoare SR, Usdin TB. (2000) The discrepancy between the binding affinity of PTH (1-34) and RS 66271 is explained by interaction of the PTH/PTHrP receptor with G-protein. J Bone Miner Res, 15 (3): 605-8. [PMID:10750577]

26. Hoare SR, Usdin TB. (2000) Tuberoinfundibular peptide (7-39) [TIP(7-39)], a novel, selective, high-affinity antagonist for the parathyroid hormone-1 receptor with no detectable agonist activity. J Pharmacol Exp Ther, 295 (2): 761-70. [PMID:11046116]

27. Hoare SR, Usdin TB. (2001) Molecular mechanisms of ligand recognition by parathyroid hormone 1 (PTH1) and PTH2 receptors. Curr Pharm Des, 7 (8): 689-713. [PMID:11375776]

28. Hopyan S, Gokgoz N, Poon R, Gensure RC, Yu C, Cole WG, Bell RS, Jüppner H, Andrulis IL, Wunder JS et al.. (2002) A mutant PTH/PTHrP type I receptor in enchondromatosis. Nat Genet, 30 (3): 306-10. [PMID:11850620]

29. Jobert AS, Zhang P, Couvineau A, Bonaventure J, Roume J, Le Merrer M, Silve C. (1998) Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia. J Clin Invest, 102 (1): 34-40. [PMID:9649554]

30. Jüppner H, Abou-Samra AB, Freeman M, Kong XF, Schipani E, Richards J, Kolakowski Jr LF, Hock J, Potts Jr JT, Kronenberg HM et al.. (1991) A G protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide. Science, 254 (5034): 1024-6. [PMID:1658941]

31. Karperien M, van der Harten HJ, van Schooten R, Farih-Sips H, den Hollander NS, Kneppers SL, Nijweide P, Papapoulos SE, Löwik CW. (1999) A frame-shift mutation in the type I parathyroid hormone (PTH)/PTH-related peptide receptor causing Blomstrand lethal osteochondrodysplasia. J Clin Endocrinol Metab, 84: 3713-3720. [PMID:10523019]

32. Kuo J, Usdin TB. (2007) Development of a rat parathyroid hormone 2 receptor antagonist. Peptides, 28 (4): 887-92. [PMID:17207559]

33. Mahon MJ, Donowitz M, Yun CC, Segre GV. (2002) Na(+)/H(+ ) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling. Nature, 417 (6891): 858-61. [PMID:12075354]

34. Maretto S, Mammi S, Bissacco E, Peggion E, Bisello A, Rosenblatt M, Chorev M, Mierke DF. (1997) Mono- and bicyclic analogs of parathyroid hormone-related protein. 2. Conformational analysis of antagonists by CD, NMR, and distance geometry calculations. Biochemistry, 36 (11): 3300-7. [PMID:9116008]

35. McDonald IM, Austin C, Buck IM, Dunstone DJ, Gaffen J, Griffin E, Harper EA, Hull RA, Kalindjian SB, Linney ID et al.. (2007) Discovery and characterization of novel, potent, non-peptide parathyroid hormone-1 receptor antagonists. J Med Chem, 50 (20): 4789-92. [PMID:17850061]

36. Mierke DF, Maretto S, Schievano E, DeLuca D, Bisello A, Mammi S, Rosenblatt M, Peggion E, Chorev M. (1997) Conformational studies of mono- and bicyclic parathyroid hormone-related protein-derived agonists. Biochemistry, 36 (34): 10372-83. [PMID:9265617]

37. Murray TM, Rao LG, Divieti P, Bringhurst FR. (2005) Parathyroid hormone secretion and action: evidence for discrete receptors for the carboxyl-terminal region and related biological actions of carboxyl- terminal ligands. Endocr Rev, 26 (1): 78-113. [PMID:15689574]

38. Nutt RF, Caulfield MP, Levy JJ, Gibbons SW, Rosenblatt M, McKee RL. (1990) Removal of partial agonism from parathyroid hormone (PTH)-related protein-(7-34)NH2 by substitution of PTH amino acids at positions 10 and 11. Endocrinology, 127 (1): 491-3. [PMID:2163325]

39. Offermanns S, Iida-Klein A, Segre GV, Simon MI. (1996) G alpha q family members couple parathyroid hormone (PTH)/PTH-related peptide and calcitonin receptors to phospholipase C in COS-7 cells. Mol Endocrinol, 10 (5): 566-74. [PMID:8732687]

40. Okazaki M, Ferrandon S, Vilardaga JP, Bouxsein ML, Potts JT, Gardella TJ. (2008) Prolonged signaling at the parathyroid hormone receptor by peptide ligands targeted to a specific receptor conformation. Proc Natl Acad Sci USA, 105 (43): 16525-30. [PMID:18946036]

41. Philbrick WM, Wysolmerski JJ, Galbraith S, Holt E, Orloff JJ, Yang KH, Vasavada RC, Weir EC, Broadus AE, Stewart AF. (1996) Defining the roles of parathyroid hormone-related protein in normal physiology. Physiol Rev, 76 (1): 127-73. [PMID:8592727]

42. Piserchio A, Usdin T, Mierke DF. (2000) Structure of tuberoinfundibular peptide of 39 residues. J Biol Chem, 275 (35): 27284-90. [PMID:10856302]

43. Potts JT Jr, Bringhurst FR, Gardella T, Nussbaum S, Segre G, Kronenberg H. (1995) Parathyroid hormone: physiology, chemistry, biosynthesis, secretion, metabolism and mode of action. In William's Textbook of Endocrinology Edited by Williams RH, Wilson JD, Foster DN (Saunders) 920-966. [ISBN:0721642640]

44. Rubin MR, Bilezikian JP. (2005) Parathyroid hormone as an anabolic skeletal therapy. Drugs, 65 (17): 2481-98. [PMID:16296873]

45. Schipani E, Kruse K, Jüppner H. (1995) A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia. Science, 268 (5207): 98-100. [PMID:7701349]

46. Segre GV, Rosenblatt M, Tully 3rd GL, Laugharn J, Reit B, Potts Jr JT. (1985) Evaluation of an in vitro parathyroid hormone antagonist in vivo in dogs. Endocrinology, 116 (3): 1024-9. [PMID:2982567]

47. Shimizu M, Carter PH, Khatri A, Potts JT, Gardella TJ. (2001) Enhanced activity in parathyroid hormone-(1-14) and -(1-11): novel peptides for probing ligand-receptor interactions. Endocrinology, 142 (7): 3068-74. [PMID:11416029]

48. Shimizu N, Guo J, Gardella TJ. (2001) Parathyroid hormone (PTH)-(1-14) and -(1-11) analogs conformationally constrained by alpha-aminoisobutyric acid mediate full agonist responses via the juxtamembrane region of the PTH-1 receptor. J Biol Chem, 276 (52): 49003-12. [PMID:11604398]

49. Strewler GJ. (2000) The physiology of parathyroid hormone-related protein. N Engl J Med, 342 (3): 177-85. [PMID:10639544]

50. Usdin TB, Bonner TI, Harta G, Mezey E. (1996) Distribution of parathyroid hormone-2 receptor messenger ribonucleic acid in rat. Endocrinology, 137 (10): 4285-97. [PMID:8828488]

51. Usdin TB, Dobolyi A, Ueda H, Palkovits M. (2003) Emerging functions for tuberoinfundibular peptide of 39 residues. Trends Endocrinol Metab, 14 (1): 14-9. [PMID:12475607]

52. Usdin TB, Gruber C, Bonner TI. (1995) Identification and functional expression of a receptor selectively recognizing parathyroid hormone, the PTH2 receptor. J Biol Chem, 270 (26): 15455-8. [PMID:7797535]

53. Usdin TB, Hoare SR, Wang T, Mezey E, Kowalak JA. (1999) TIP39: a new neuropeptide and PTH2-receptor agonist from hypothalamus. Nat Neurosci, 2 (11): 941-3. [PMID:10526330]

54. Usdin TB, Wang T, Hoare SR, Mezey E, Palkovits M. (2000) New members of the parathyroid hormone/parathyroid hormone receptor family: the parathyroid hormone 2 receptor and tuberoinfundibular peptide of 39 residues. Front Neuroendocrinol, 21 (4): 349-83. [PMID:11013069]

55. Vilardaga JP, Gardella TJ, Wehbi VL, Feinstein TN. (2012) Non-canonical signaling of the PTH receptor. Trends Pharmacol Sci, 33 (8): 423-31. [PMID:22709554]

56. Vilardaga JP, Jean-Alphonse FG, Gardella TJ. (2014) Endosomal generation of cAMP in GPCR signaling. Nat Chem Biol, 10 (9): 700-6. [PMID:25271346]

57. Vilardaga JP, Krasel C, Chauvin S, Bambino T, Lohse MJ, Nissenson RA. (2002) Internalization determinants of the parathyroid hormone receptor differentially regulate beta-arrestin/receptor association. J Biol Chem, 277 (10): 8121-9. [PMID:11726668]

58. Vilardaga JP, Romero G, Friedman PA, Gardella TJ. (2011) Molecular basis of parathyroid hormone receptor signaling and trafficking: a family B GPCR paradigm. Cell Mol Life Sci, 68 (1): 1-13. [PMID:20703892]

59. Wang B, Ardura JA, Romero G, Yang Y, Hall RA, Friedman PA. (2010) Na/H exchanger regulatory factors control parathyroid hormone receptor signaling by facilitating differential activation of G(alpha) protein subunits. J Biol Chem, 285 (35): 26976-86. [PMID:20562104]

60. Wehbi VL, Stevenson HP, Feinstein TN, Calero G, Romero G, Vilardaga JP. (2013) Noncanonical GPCR signaling arising from a PTH receptor-arrestin-Gβγ complex. Proc Natl Acad Sci USA, 110 (4): 1530-5. [PMID:23297229]

61. Yamaguchi T, Hosomichi K, Narita A, Shirota T, Tomoyasu Y, Maki K, Inoue I. (2011) Exome resequencing combined with linkage analysis identifies novel PTH1R variants in primary failure of tooth eruption in Japanese. J Bone Miner Res, 26 (7): 1655-61. [PMID:21404329]

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