KEGG   PATHWAY: mni04928
Entry
mni04928                    Pathway                                
Name
Parathyroid hormone synthesis, secretion and action - Macaca nemestrina (pig-tailed macaque)
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
mni04928  Parathyroid hormone synthesis, secretion and action
mni04928

Organism
Macaca nemestrina (pig-tailed macaque) [GN:mni]
Gene
105470290  CASR; extracellular calcium-sensing receptor [KO:K04612]
105475385  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
105479273  GNAI3; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
105480474  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
105494232  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
105489474  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
105479810  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
105477872  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
105470270  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
105492900  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
105492251  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
105492815  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
105467851  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
105498714  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
105485659  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
105469511  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
105481530  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
105481533  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
105492354  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
105477623  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
105492154  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
105474470  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
105490848  GCM1; chorion-specific transcription factor GCMa isoform X1 [KO:K21598]
105482626  GCM2; chorion-specific transcription factor GCMb [KO:K21598]
105496353  MAFB; transcription factor MafB [KO:K09036]
105494343  GATA3; trans-acting T-cell-specific transcription factor GATA-3 isoform X1 [KO:K17895]
105474275  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
105470057  VDR; vitamin D3 receptor isoform X1 [KO:K08539]
105471885  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
105474442  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
105492958  RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526]
105484150  FGF23; fibroblast growth factor 23 [KO:K22428]
105476567  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
105486003  KL; klotho [KO:K14756] [EC:3.2.1.31]
105480656  MAPK1; LOW QUALITY PROTEIN: mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105482882  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105467076  EGR1; early growth response protein 1 [KO:K09203]
105486912  PTH; parathyroid hormone [KO:K05261]
105465645  SGK1; serine/threonine-protein kinase Sgk1 isoform X1 [KO:K13302] [EC:2.7.11.1]
105498871  WNK2; serine/threonine-protein kinase WNK2 isoform X1 [KO:K08867] [EC:2.7.11.1]
105493799  WNK3; LOW QUALITY PROTEIN: serine/threonine-protein kinase WNK3 [KO:K08867] [EC:2.7.11.1]
105472093  WNK4; serine/threonine-protein kinase WNK4 isoform X2 [KO:K08867] [EC:2.7.11.1]
105484099  WNK1; serine/threonine-protein kinase WNK1 isoform X1 [KO:K08867] [EC:2.7.11.1]
105480198  OXSR1; serine/threonine-protein kinase OSR1 isoform X1 [KO:K08835] [EC:2.7.11.1]
105483292  STK39; STE20/SPS1-related proline-alanine-rich protein kinase isoform X1 [KO:K08835] [EC:2.7.11.1]
105494041  SLC12A3; LOW QUALITY PROTEIN: solute carrier family 12 member 3 [KO:K14426]
105492179  PTHLH; parathyroid hormone-related protein [KO:K22608]
105480375  PTH1R; parathyroid hormone/parathyroid hormone-related peptide receptor isoform X1 [KO:K04585]
105469029  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
105485029  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
105497021  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
105471195  TRPV5; transient receptor potential cation channel subfamily V member 5 isoform X1 [KO:K04974]
105487825  SLC34A2; sodium-dependent phosphate transport protein 2B isoform X1 [KO:K14683]
105471980  SLC34A3; sodium-dependent phosphate transport protein 2C isoform X1 [KO:K14683]
105484053  SLC34A1; sodium-dependent phosphate transport protein 2A isoform X1 [KO:K14683]
105469134  SLC9A3R1; Na(+)/H(+) exchange regulatory cofactor NHE-RF1 [KO:K13365]
105470579  neuroendocrine secretory protein 55 [KO:K04632]
105470577  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
105487686  PDE4C; cAMP-specific 3',5'-cyclic phosphodiesterase 4C isoform X1 [KO:K13293] [EC:3.1.4.53]
105498452  PDE4B; cAMP-specific 3',5'-cyclic phosphodiesterase 4B isoform X1 [KO:K13293] [EC:3.1.4.53]
105499433  PDE4D; cAMP-specific 3',5'-cyclic phosphodiesterase 4D isoform X1 [KO:K13293] [EC:3.1.4.53]
105486933  PDE4A; cAMP-specific 3',5'-cyclic phosphodiesterase 4A [KO:K13293] [EC:3.1.4.53]
105498103  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
105491778  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
105482741  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105474079  25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial isoform X1 [KO:K07438] [EC:1.14.15.18]
105470644  1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial [KO:K07436] [EC:1.14.15.16]
105479408  MEF2A; myocyte-specific enhancer factor 2A isoform X1 [KO:K09260]
105491929  MEF2C; myocyte-specific enhancer factor 2C isoform X1 [KO:K04454]
105498054  MEF2D; myocyte-specific enhancer factor 2D isoform X1 [KO:K09262]
105469492  SOST; sclerostin [KO:K16834]
105493223  NR4A2; nuclear receptor subfamily 4 group A member 2 isoform X1 [KO:K08558]
105474128  NACA; nascent polypeptide-associated complex subunit alpha isoform X2 [KO:K03626]
105476043  LOW QUALITY PROTEIN: nascent polypeptide-associated complex subunit alpha-like [KO:K03626]
105476848  NACA2; LOW QUALITY PROTEIN: nascent polypeptide-associated complex subunit alpha-2 [KO:K03626]
105487405  JUND; transcription factor jun-D [KO:K04449]
105498040  BGLAP; osteocalcin [KO:K22609]
105469707  LRP5; LOW QUALITY PROTEIN: low-density lipoprotein receptor-related protein 5 [KO:K03068]
105482314  LRP6; low-density lipoprotein receptor-related protein 6 [KO:K03068]
105468005  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
105483203  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
105485736  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
105487183  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
105497957  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
105471318  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
105471659  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X3 [KO:K09048]
105464416  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105475779  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
105497591  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
105491723  TNFSF11; tumor necrosis factor ligand superfamily member 11 isoform X1 [KO:K05473]
105477002  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
105474528  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
105495778  FOS; proto-oncogene c-Fos [KO:K04379]
105489529  RUNX2; runt-related transcription factor 2 isoform X2 [KO:K09278]
105493702  MMP13; collagenase 3 [KO:K07994] [EC:3.4.24.-]
105483392  GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346]
105469013  GNA13; guanine nucleotide-binding protein subunit alpha-13 isoform X1 [KO:K04639]
105495278  ARHGEF1; rho guanine nucleotide exchange factor 1 [KO:K12330]
105498081  ARHGEF11; rho guanine nucleotide exchange factor 11 isoform X1 [KO:K12331]
105488365  AKAP13; A-kinase anchor protein 13 isoform X2 [KO:K16529]
105480439  RHOA; transforming protein RhoA [KO:K04513]
105465688  PLD1; LOW QUALITY PROTEIN: phospholipase D1 [KO:K01115] [EC:3.1.4.4]
105472332  PLD2; phospholipase D2 isoform X2 [KO:K01115] [EC:3.1.4.4]
105468761  ARRB1; beta-arrestin-1 isoform X1 [KO:K04439]
105472261  ARRB2; beta-arrestin-2 isoform X3 [KO:K04439]
105463916  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
105471274  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
105477727  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105488275  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105499628  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
105491522  MMP15; matrix metalloproteinase-15 [KO:K07995] [EC:3.4.24.-]
105497291  MMP16; matrix metalloproteinase-16 [KO:K07996] [EC:3.4.24.-]
105490543  MMP17; matrix metalloproteinase-17 isoform X1 [KO:K07997] [EC:3.4.24.-]
105496258  MMP24; matrix metalloproteinase-24 isoform X1 [KO:K08002] [EC:3.4.24.-]
105467888  MMP25; matrix metalloproteinase-25 isoform X1 [KO:K08003] [EC:3.4.24.-]
105467043  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
105493061  EGFR; epidermal growth factor receptor isoform X1 [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
mni04012  ErbB signaling pathway
mni04020  Calcium signaling pathway
mni04024  cAMP signaling pathway
mni04310  Wnt signaling pathway
mni04380  Osteoclast differentiation
mni04961  Endocrine and other factor-regulated calcium reabsorption
KO pathway
ko04928   
LinkDB

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