KEGG   PATHWAY: mun04928
Entry
mun04928                    Pathway                                
Name
Parathyroid hormone synthesis, secretion and action - Meriones unguiculatus (Mongolian gerbil)
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
mun04928  Parathyroid hormone synthesis, secretion and action
mun04928

Organism
Meriones unguiculatus (Mongolian gerbil) [GN:mun]
Gene
110541014  Casr; extracellular calcium-sensing receptor [KO:K04612]
110539607  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
110545517  Gnai3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
110564775  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
110555169  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
110550962  Adcy2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
110555185  Adcy3; adenylate cyclase type 3 isoform X3 [KO:K08043] [EC:4.6.1.1]
110556521  Adcy4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
110547229  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
110559444  Adcy6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
110560723  Adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
110561696  Adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
110545944  Adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
110562511  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
110548534  Gna11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
110563159  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
110555720  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
110551595  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
110550598  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
110552142  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
110558908  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
110543748  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
110554611  Gcm2; chorion-specific transcription factor GCMb [KO:K21598]
110560502  Gcm1; chorion-specific transcription factor GCMa [KO:K21598]
110552798  Mafb; transcription factor MafB [KO:K09036]
110545620  Gata3; trans-acting T-cell-specific transcription factor GATA-3 isoform X2 [KO:K17895]
110552322  Sp1; transcription factor Sp1 isoform X1 [KO:K04684]
110546178  Vdr; vitamin D3 receptor [KO:K08539]
110549176  Rxra; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
110543383  Rxrb; retinoic acid receptor RXR-beta isoform X2 [KO:K08525]
110551800  Rxrg; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
110548635  Fgf23; fibroblast growth factor 23 [KO:K22428]
110563307  Fgfr1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
110553796  Mapk1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
110547978  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
110558474  Egr1; LOW QUALITY PROTEIN: early growth response protein 1 [KO:K09203]
110562910  Pth; parathyroid hormone [KO:K05261]
110550419  Sgk1; serine/threonine-protein kinase Sgk1 isoform X2 [KO:K13302] [EC:2.7.11.1]
110550897  Wnk4; serine/threonine-protein kinase WNK4 isoform X1 [KO:K08867] [EC:2.7.11.1]
110546052  Wnk1; serine/threonine-protein kinase WNK1 isoform X24 [KO:K08867] [EC:2.7.11.1]
110549223  Wnk2; serine/threonine-protein kinase WNK2 isoform X1 [KO:K08867] [EC:2.7.11.1]
110542466  Wnk3; serine/threonine-protein kinase WNK3 isoform X1 [KO:K08867] [EC:2.7.11.1]
110555049  Oxsr1; serine/threonine-protein kinase OSR1 [KO:K08835] [EC:2.7.11.1]
110560959  Slc12a3; solute carrier family 12 member 3 isoform X1 [KO:K14426]
110553825  Pthlh; LOW QUALITY PROTEIN: parathyroid hormone-related protein [KO:K22608]
110554983  Pth1r; parathyroid hormone/parathyroid hormone-related peptide receptor isoform X2 [KO:K04585]
110555335  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
110559612  Prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
110556016  Prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
110558950  Trpv5; transient receptor potential cation channel subfamily V member 5 [KO:K04974]
110552770  Slc34a2; sodium-dependent phosphate transport protein 2B [KO:K14683]
110549772  Slc34a1; sodium-dependent phosphate transport protein 2A [KO:K14683]
110557037  Slc34a3; sodium-dependent phosphate transport protein 2C [KO:K14683]
110547585  Nherf1; Na(+)/H(+) exchange regulatory cofactor NHE-RF1 [KO:K13365]
110563608  neuroendocrine secretory protein 55-like [KO:K04632]
110562135  Pde4d; cAMP-specific 3',5'-cyclic phosphodiesterase 4D isoform X7 [KO:K13293] [EC:3.1.4.53]
110555768  Pde4a; cAMP-specific 3',5'-cyclic phosphodiesterase 4A isoform X1 [KO:K13293] [EC:3.1.4.53]
110549146  Pde4c; cAMP-specific 3',5'-cyclic phosphodiesterase 4C isoform X4 [KO:K13293] [EC:3.1.4.53]
110562364  Pde4b; cAMP-specific 3',5'-cyclic phosphodiesterase 4B isoform X1 [KO:K13293] [EC:3.1.4.53]
110545842  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
110555016  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
110561784  25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial [KO:K07438] [EC:1.14.15.18]
110545262  1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial [KO:K07436] [EC:1.14.15.16]
110556955  Mef2a; myocyte-specific enhancer factor 2A isoform X1 [KO:K09260]
110539611  Mef2c; myocyte-specific enhancer factor 2C isoform X1 [KO:K04454]
110548981  Mef2d; myocyte-specific enhancer factor 2D isoform X1 [KO:K09262]
110551876  Sost; sclerostin [KO:K16834]
110557168  Nr4a2; nuclear receptor subfamily 4 group A member 2 isoform X1 [KO:K08558]
110548974  Naca; nascent polypeptide-associated complex subunit alpha [KO:K03626]
110549151  Jund; transcription factor JunD [KO:K04449]
110549007  Bglap; osteocalcin [KO:K22609]
110547061  Lrp5; low-density lipoprotein receptor-related protein 5 isoform X1 [KO:K03068]
110551009  Lrp6; low-density lipoprotein receptor-related protein 6 isoform X1 [KO:K03068]
110551437  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
110556579  Atf2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
110549859  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
110555614  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
110549233  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
110554250  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
110561882  Creb3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
110564629  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
110554970  Creb5; cyclic AMP-responsive element-binding protein 5 isoform X2 [KO:K09047]
110565383  Atf6b; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
110562414  Tnfsf11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
110557800  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
110546586  Cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
110546962  Fos; protein c-Fos [KO:K04379]
110555956  Runx2; runt-related transcription factor 2 isoform X3 [KO:K09278]
110558087  Mmp13; collagenase 3 [KO:K07994] [EC:3.4.24.-]
110554732  Gna12; guanine nucleotide-binding protein subunit alpha-12 isoform X2 [KO:K04346]
110560037  Gna13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
110566357  Arhgef1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
110564974  Arhgef11; rho guanine nucleotide exchange factor 11 isoform X3 [KO:K12331]
110566614  Akap13; A-kinase anchor protein 13 isoform X1 [KO:K16529]
110540728  transforming protein RhoA-like isoform X1 [KO:K04513]
110565123  Rhoa; transforming protein RhoA isoform X2 [KO:K04513]
110553679  Pld1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
110557322  Pld2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
110560411  Arrb1; beta-arrestin-1 isoform X3 [KO:K04439]
110557323  Arrb2; beta-arrestin-2 isoform X1 [KO:K04439]
110541705  Araf; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
110545779  Braf; serine/threonine-protein kinase B-raf isoform X8 [KO:K04365] [EC:2.7.11.1]
110550814  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
110559000  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110550039  Mmp14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
110551176  Mmp15; matrix metalloproteinase-15 [KO:K07995] [EC:3.4.24.-]
110556311  Mmp16; matrix metalloproteinase-16 [KO:K07996] [EC:3.4.24.-]
110563265  Mmp17; matrix metalloproteinase-17 isoform X1 [KO:K07997] [EC:3.4.24.-]
110550559  Mmp24; matrix metalloproteinase-24 isoform X1 [KO:K08002] [EC:3.4.24.-]
110545952  Mmp25; matrix metalloproteinase-25 isoform X1 [KO:K08003] [EC:3.4.24.-]
110557378  Hbegf; proheparin-binding EGF-like growth factor [KO:K08523]
110539539  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
PMID:27065162
  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
PMID:28363951
  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
PMID:20703892
  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
PMID:29291826
  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
PMID:25917456
  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
PMID:22622503
  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
PMID:20010546
  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
PMID:27194212
  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
PMID:21576356
  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
PMID:17975663
  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
PMID:22628548
  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
PMID:21097685
  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
PMID:11698670
  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
PMID:20074973
  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
PMID:17696759
  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
PMID:24940803
  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
PMID:29413898
  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
PMID:12364326
  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
PMID:19716455
  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
PMID:17517365
  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
PMID:16164977
  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
PMID:11274169
  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
PMID:15705779
  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
PMID:12738761
  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
PMID:17107942
  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
PMID:32982979
  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
PMID:27622885
  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
PMID:33491560
  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
mun04012  ErbB signaling pathway
mun04020  Calcium signaling pathway
mun04024  cAMP signaling pathway
mun04310  Wnt signaling pathway
mun04380  Osteoclast differentiation
mun04961  Endocrine and other factor-regulated calcium reabsorption
KO pathway
ko04928   
LinkDB

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