KEGG   PATHWAY: tup04928
Entry
tup04928                    Pathway                                
Name
Parathyroid hormone synthesis, secretion and action - Tupaia chinensis (Chinese tree shrew)
Description
Parathyroid hormone (PTH) is a key regulator of calcium and phosphorus homeostasis. The principal regulators of PTH secretion are extracellular ionized calcium (Ca2+) and 1,25-dihydroxyvitamin D (1,25(OH)2D3). Under conditions of dietary Ca restriction, a decrement in serum Ca concentration induces release of PTH from the parathyroid gland. PTH acts on bone and kidney to stimulate bone turnover, increase the circulating levels of 1,25(OH)2D3 and calcium and inhibit the reabsorption of phosphate from the glomerular filtrate. This hormone exerts its actions via binding to the PTH/PTH-related peptide receptor (PTH1R). PTH1R primarily activates two sub-types of heterotrimeric Gproteins: Gs and Gq , which in turn regulate the activity of adenylyl cyclases and phospholipase C (PLC) that control the flow of cAMP/PKA and IP/PKC signaling cascades, respectively.
Class
Organismal Systems; Endocrine system
Pathway map
tup04928  Parathyroid hormone synthesis, secretion and action
tup04928

Organism
Tupaia chinensis (Chinese tree shrew) [GN:tup]
Gene
102477960  CASR; calcium sensing receptor [KO:K04612]
102476737  GNAI3; G protein subunit alpha i3 [KO:K04630]
102479323  GNAI1; G protein subunit alpha i1 [KO:K04630]
102475420  GNAI2; G protein subunit alpha i2 [KO:K04630]
102468873  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
102492353  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
102477532  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
102490273  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
102490639  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
102468478  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
102496578  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
102472317  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
102477344  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
102468263  GNAQ; G protein subunit alpha q [KO:K04634]
102479071  GNA11; G protein subunit alpha 11 [KO:K04635]
102477438  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
102476196  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
102472532  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
102492903  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
102473622  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102482868  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102475587  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102480693  GCM1; glial cells missing homolog 1 [KO:K21598]
102481031  GCM2; glial cells missing homolog 2 [KO:K21598]
102488897  MAFB; MAF bZIP transcription factor B [KO:K09036]
102492135  GATA3; GATA binding protein 3 [KO:K17895]
102473003  SP1; Sp1 transcription factor [KO:K04684]
102503250  VDR; vitamin D (1,25- dihydroxyvitamin D3) receptor [KO:K08539]
102470277  RXRA; retinoid X receptor alpha [KO:K08524]
102495243  RXRB; retinoid X receptor beta [KO:K08525]
102478064  RXRG; retinoid X receptor gamma [KO:K08526]
102479073  FGF23; fibroblast growth factor 23 [KO:K22428]
102484087  FGFR1; fibroblast growth factor receptor 1 [KO:K04362] [EC:2.7.10.1]
102470766  KL; klotho [KO:K14756] [EC:3.2.1.31]
102496453  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102483057  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102500322  EGR1; early growth response 1 [KO:K09203]
102476809  PTH; parathyroid hormone [KO:K05261]
102499967  SGK1; serum/glucocorticoid regulated kinase 1 [KO:K13302] [EC:2.7.11.1]
102487865  WNK4; WNK lysine deficient protein kinase 4 [KO:K08867] [EC:2.7.11.1]
102502762  WNK2; WNK lysine deficient protein kinase 2 [KO:K08867] [EC:2.7.11.1]
102478115  WNK1; WNK lysine deficient protein kinase 1 [KO:K08867] [EC:2.7.11.1]
102491711  WNK3; WNK lysine deficient protein kinase 3 [KO:K08867] [EC:2.7.11.1]
102485906  STK39; serine/threonine kinase 39 [KO:K08835] [EC:2.7.11.1]
102470021  OXSR1; oxidative stress responsive 1 [KO:K08835] [EC:2.7.11.1]
102489205  SLC12A3; solute carrier family 12 member 3 [KO:K14426]
102479070  PTHLH; parathyroid hormone like hormone [KO:K22608]
102475271  PTH1R; parathyroid hormone 1 receptor [KO:K04585]
102495954  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
102469271  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
102497204  PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
102501068  TRPV5; transient receptor potential cation channel subfamily V member 5 [KO:K04974]
102475679  SLC34A2; solute carrier family 34 member 2 [KO:K14683]
102473472  SLC34A1; solute carrier family 34 member 1 [KO:K14683]
102478722  SLC34A3; solute carrier family 34 member 3 [KO:K14683]
102469825  SLC9A3R1; SLC9A3 regulator 1 [KO:K13365]
102489563  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
102501321  neuroendocrine secretory protein 55 [KO:K04632]
102491532  PDE4A; phosphodiesterase 4A [KO:K13293] [EC:3.1.4.53]
102483694  PDE4B; phosphodiesterase 4B [KO:K13293] [EC:3.1.4.53]
102468572  PDE4C; phosphodiesterase 4C [KO:K13293] [EC:3.1.4.53]
102488531  PDE4D; phosphodiesterase 4D [KO:K13293] [EC:3.1.4.53]
102502506  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
102478525  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102492875  25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial [KO:K07438] [EC:1.14.15.18]
102471055  1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial [KO:K07436] [EC:1.14.15.16]
102473058  MEF2A; myocyte enhancer factor 2A [KO:K09260]
102499043  MEF2C; myocyte enhancer factor 2C [KO:K04454]
102501286  MEF2D; myocyte-specific enhancer factor 2D [KO:K09262]
102475233  SOST; sclerostin [KO:K16834]
102472863  NR4A2; nuclear receptor subfamily 4 group A member 2 [KO:K08558]
102484309  NACA; nascent polypeptide-associated complex alpha subunit [KO:K03626]
102494928  BGLAP; bone gamma-carboxyglutamate protein [KO:K22609]
102502071  LRP6; LDL receptor related protein 6 [KO:K03068]
102473447  LRP5L; LDL receptor related protein 5 like [KO:K03068]
102500092  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
102473406  ATF2; activating transcription factor 2 [KO:K04450]
102491362  CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048]
102471928  CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048]
102469074  CREB3; cAMP responsive element binding protein 3 [KO:K09048]
102468245  cyclic AMP-responsive element-binding protein 3-like [KO:K09048]
102494703  CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048]
102484102  CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048]
102478154  ATF4; activating transcription factor 4 [KO:K04374]
102487006  CREB5; cAMP responsive element binding protein 5 [KO:K09047]
102484080  ATF6B; activating transcription factor 6 beta [KO:K09049]
102487682  TNFSF11; tumor necrosis factor superfamily member 11 [KO:K05473]
102474592  BCL2; BCL2, apoptosis regulator [KO:K02161]
102490159  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
102491199  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
102494351  RUNX2; runt related transcription factor 2 [KO:K09278]
102488239  MMP13; matrix metallopeptidase 13 [KO:K07994] [EC:3.4.24.-]
102501406  GNA12; G protein subunit alpha 12 [KO:K04346]
102488219  GNA13; G protein subunit alpha 13 [KO:K04639]
102484536  ARHGEF1; Rho guanine nucleotide exchange factor 1 [KO:K12330]
102475544  ARHGEF11; Rho guanine nucleotide exchange factor 11 [KO:K12331]
102501180  AKAP13; A-kinase anchoring protein 13 [KO:K16529]
102487039  RHOA; ras homolog family member A [KO:K04513]
102495205  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
102499889  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
102491217  ARRB1; arrestin beta 1 [KO:K04439]
102497124  ARRB2; arrestin beta 2 [KO:K04439]
102493239  ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
102477389  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
102497488  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102476496  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102468813  MMP14; matrix metallopeptidase 14 [KO:K07763] [EC:3.4.24.80]
102470396  MMP15; matrix metallopeptidase 15 [KO:K07995] [EC:3.4.24.-]
102487906  MMP16; matrix metallopeptidase 16 [KO:K07996] [EC:3.4.24.-]
102477680  MMP17; matrix metallopeptidase 17 [KO:K07997] [EC:3.4.24.-]
102482181  MMP24; matrix metallopeptidase 24 [KO:K08002] [EC:3.4.24.-]
102473778  MMP25; matrix metallopeptidase 25 [KO:K08003] [EC:3.4.24.-]
102498262  HBEGF; heparin binding EGF like growth factor [KO:K08523]
102485304  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
Compound
C00009  Orthophosphate
C00020  AMP
C00076  Calcium cation
C00165  Diacylglycerol
C00575  3',5'-Cyclic AMP
C00698  Cl-
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C01561  Calcidiol
C01673  Calcitriol
C18231  Calcitetrol
Reference
  Authors
Khundmiri SJ, Murray RD, Lederer E
  Title
PTH and Vitamin D.
  Journal
Compr Physiol 6:561-601 (2016)
DOI:10.1002/cphy.c140071
Reference
  Authors
Bastepe M, Turan S, He Q
  Title
Heterotrimeric G proteins in the control of parathyroid hormone actions.
  Journal
J Mol Endocrinol 58:R203-R224 (2017)
DOI:10.1530/JME-16-0221
Reference
  Authors
Vilardaga JP, Romero G, Friedman PA, Gardella TJ
  Title
Molecular basis of parathyroid hormone receptor signaling and trafficking: a family B GPCR paradigm.
  Journal
Cell Mol Life Sci 68:1-13 (2011)
DOI:10.1007/s00018-010-0465-9
Reference
  Authors
Naveh-Many T, Silver J
  Title
Transcription factors that determine parathyroid development power PTH expression.
  Journal
Kidney Int 93:7-9 (2018)
DOI:10.1016/j.kint.2017.08.026
Reference
  Authors
Han SI, Tsunekage Y, Kataoka K
  Title
Gata3 cooperates with Gcm2 and MafB to activate parathyroid hormone gene expression by interacting with SP1.
  Journal
Mol Cell Endocrinol 411:113-20 (2015)
DOI:10.1016/j.mce.2015.04.018
Reference
  Authors
Ferre S, Hoenderop JG, Bindels RJ
  Title
Sensing mechanisms involved in Ca2+ and Mg2+ homeostasis.
  Journal
Kidney Int 82:1157-66 (2012)
DOI:10.1038/ki.2012.179
Reference
  Authors
Komaba H, Fukagawa M
  Title
FGF23-parathyroid interaction: implications in chronic kidney disease.
  Journal
Kidney Int 77:292-8 (2010)
DOI:10.1038/ki.2009.466
Reference
  Authors
Bilezikian JP, Cusano NE, Khan AA, Liu JM, Marcocci C, Bandeira F
  Title
Primary hyperparathyroidism.
  Journal
Nat Rev Dis Primers 2:16033 (2016)
DOI:10.1038/nrdp.2016.33
Reference
  Authors
de Groot T, Kovalevskaya NV, Verkaart S, Schilderink N, Felici M, van der Hagen EA, Bindels RJ, Vuister GW, Hoenderop JG
  Title
Molecular mechanisms of calmodulin action on TRPV5 and modulation by parathyroid hormone.
  Journal
Mol Cell Biol 31:2845-53 (2011)
DOI:10.1128/MCB.01319-10
Reference
  Authors
Hernando N, Wagner C, Biber J, Murer H
  Title
Kidney kinase network regulates renal ion cotransport.
  Journal
J Clin Invest 117:3179-82 (2007)
DOI:10.1172/JCI33859
Reference
  Authors
Wang B, Means CK, Yang Y, Mamonova T, Bisello A, Altschuler DL, Scott JD, Friedman PA
  Title
Ezrin-anchored protein kinase A coordinates phosphorylation-dependent disassembly of a NHERF1 ternary complex to regulate hormone-sensitive phosphate transport.
  Journal
J Biol Chem 287:24148-63 (2012)
DOI:10.1074/jbc.M112.369405
Reference
  Authors
Crenshaw TD, Rortvedt LA, Hassen Z
  Title
Triennial Growth Symposium: a novel pathway for vitamin D-mediated phosphate homeostasis: implications for skeleton growth and mineralization.
  Journal
J Anim Sci 89:1957-64 (2011)
DOI:10.2527/jas.2010-3411
Reference
  Authors
Zierold C, Mings JA, DeLuca HF
  Title
Parathyroid hormone regulates 25-hydroxyvitamin D(3)-24-hydroxylase mRNA by altering its stability.
  Journal
Proc Natl Acad Sci U S A 98:13572-6 (2001)
DOI:10.1073/pnas.241516798
Reference
  Authors
Kramer I, Keller H, Leupin O, Kneissel M
  Title
Does osteocytic SOST suppression mediate PTH bone anabolism?
  Journal
Trends Endocrinol Metab 21:237-44 (2010)
DOI:10.1016/j.tem.2009.12.002
Reference
  Authors
Leupin O, Kramer I, Collette NM, Loots GG, Natt F, Kneissel M, Keller H
  Title
Control of the SOST bone enhancer by PTH using MEF2 transcription factors.
  Journal
J Bone Miner Res 22:1957-67 (2007)
DOI:10.1359/jbmr.070804
Reference
  Authors
Meir T, Durlacher K, Pan Z, Amir G, Richards WG, Silver J, Naveh-Many T
  Title
Parathyroid hormone activates the orphan nuclear receptor Nurr1 to induce FGF23 transcription.
  Journal
Kidney Int 86:1106-15 (2014)
DOI:10.1038/ki.2014.215
Reference
  Authors
Pellicelli M, Hariri H, Miller JA, St-Arnaud R
  Title
Lrp6 is a target of the PTH-activated alphaNAC transcriptional coregulator.
  Journal
Biochim Biophys Acta 1861:61-71 (2018)
DOI:10.1016/j.bbagrm.2018.01.008
Reference
  Authors
Fu Q, Jilka RL, Manolagas SC, O'Brien CA
  Title
Parathyroid hormone stimulates receptor activator of NFkappa B ligand and inhibits osteoprotegerin expression via protein kinase A activation of cAMP-response element-binding protein.
  Journal
J Biol Chem 277:48868-75 (2002)
DOI:10.1074/jbc.M208494200
Reference
  Authors
O'Brien CA
  Title
Control of RANKL gene expression.
  Journal
Bone 46:911-9 (2010)
DOI:10.1016/j.bone.2009.08.050
Reference
  Authors
Jilka RL
  Title
Molecular and cellular mechanisms of the anabolic effect of intermittent PTH.
  Journal
Bone 40:1434-46 (2007)
DOI:10.1016/j.bone.2007.03.017
Reference
PMID:8810350
  Authors
Pearman AT, Chou WY, Bergman KD, Pulumati MR, Partridge NC
  Title
Parathyroid hormone induces c-fos promoter activity in osteoblastic cells through phosphorylated cAMP response element (CRE)-binding protein binding to the major CRE.
  Journal
J Biol Chem 271:25715-21 (1996)
DOI:10.1074/jbc.271.41.25715
Reference
  Authors
Boumah CE, Selvamurugan N, Partridge NC
  Title
Transcription in the osteoblast: regulatory mechanisms utilized by parathyroid hormone and transforming growth factor-beta.
  Journal
Prog Nucleic Acid Res Mol Biol 80:287-321 (2005)
DOI:10.1016/S0079-6603(05)80007-8
Reference
  Authors
Hess J, Porte D, Munz C, Angel P
  Title
AP-1 and Cbfa/runt physically interact and regulate parathyroid hormone-dependent MMP13 expression in osteoblasts through a new osteoblast-specific element 2/AP-1  composite element.
  Journal
J Biol Chem 276:20029-38 (2001)
DOI:10.1074/jbc.M010601200
Reference
  Authors
Singh AT, Gilchrist A, Voyno-Yasenetskaya T, Radeff-Huang JM, Stern PH
  Title
G alpha12/G alpha13 subunits of heterotrimeric G proteins mediate parathyroid hormone activation of phospholipase D in UMR-106 osteoblastic cells.
  Journal
Endocrinology 146:2171-5 (2005)
DOI:10.1210/en.2004-1283
Reference
  Authors
Ahmed I, Gesty-Palmer D, Drezner MK, Luttrell LM
  Title
Transactivation of the epidermal growth factor receptor mediates parathyroid hormone and prostaglandin F2 alpha-stimulated mitogen-activated protein kinase activation in cultured transgenic murine osteoblasts.
  Journal
Mol Endocrinol 17:1607-21 (2003)
DOI:10.1210/me.2002-0040
Reference
  Authors
Sneddon WB, Yang Y, Ba J, Harinstein LM, Friedman PA
  Title
Extracellular signal-regulated kinase activation by parathyroid hormone in distal tubule cells.
  Journal
Am J Physiol Renal Physiol 292:F1028-34 (2007)
DOI:10.1152/ajprenal.00288.2006
Reference
  Authors
Agoro R, Ni P, Noonan ML, White KE
  Title
Osteocytic FGF23 and Its Kidney Function.
  Journal
Front Endocrinol (Lausanne) 11:592 (2020)
DOI:10.3389/fendo.2020.00592
Reference
  Authors
Erben RG, Andrukhova O
  Title
FGF23-Klotho signaling axis in the kidney.
  Journal
Bone 100:62-68 (2017)
DOI:10.1016/j.bone.2016.09.010
Reference
  Authors
Murillo-de-Ozores AR, Rodriguez-Gama A, Carbajal-Contreras H, Gamba G, Castaneda-Bueno M
  Title
WNK4 kinase: from structure to physiology.
  Journal
Am J Physiol Renal Physiol 320:F378-F403 (2021)
DOI:10.1152/ajprenal.00634.2020
Related
pathway
tup04012  ErbB signaling pathway
tup04020  Calcium signaling pathway
tup04024  cAMP signaling pathway
tup04310  Wnt signaling pathway
tup04380  Osteoclast differentiation
tup04961  Endocrine and other factor-regulated calcium reabsorption
KO pathway
ko04928   
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