Entry Name Parathyroid hormone synthesis, secretion and action
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 systemBRITE hierarchy
Pathway map ko04928 Parathyroid hormone synthesis, secretion and action
Orthology K02161 BCL2; apoptosis regulator Bcl-2
K03068 LRP5_6; low density lipoprotein receptor-related protein 5/6
K03626 EGD2, NACA; nascent polypeptide-associated complex subunit alpha
K04346 GNA12; guanine nucleotide-binding protein subunit alpha-12
K04362 FGFR1, CD331; fibroblast growth factor receptor 1 [EC:2.7.10.1 ]
K04365 BRAF; B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04366 RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04368 MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2 ]
K04374 ATF4, CREB2; cyclic AMP-dependent transcription factor ATF-4
K04379 FOS; proto-oncogene protein c-fos
K04449 JUND; transcription factor jun-D
K04450 ATF2, CREBP1; cyclic AMP-dependent transcription factor ATF-2
K04454 MEF2C; MADS-box transcription enhancer factor 2C
K04513 RHOA; Ras homolog gene family, member A
K04585 PTH1R, PTHR1; parathyroid hormone receptor 1
K04612 CASR; calcium-sensing receptor
K04630 GNAI; guanine nucleotide-binding protein G(i) subunit alpha
K04632 GNAS; guanine nucleotide-binding protein G(s) subunit alpha
K04634 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha
K04635 GNA11; guanine nucleotide-binding protein subunit alpha-11
K04639 GNA13; guanine nucleotide-binding protein subunit alpha-13
K04684 SP1; transcription factor Sp1
K04958 ITPR1; inositol 1,4,5-triphosphate receptor type 1
K04959 ITPR2; inositol 1,4,5-triphosphate receptor type 2
K04960 ITPR3; inositol 1,4,5-triphosphate receptor type 3
K04974 TRPV5; transient receptor potential cation channel subfamily V member 5
K05261 PTH; parathyroid hormone
K05473 TNFSF11, RANKL, CD254; tumor necrosis factor ligand superfamily member 11
K05870 CREB1; cyclic AMP-responsive element-binding protein 1
K06625 CDKN1A, P21, CIP1; cyclin-dependent kinase inhibitor 1A
K07438 CYP27B1; calcidiol 1-monooxygenase (25-hydroxyvitamin D3 1alpha-hydroxylase) [EC:1.14.15.18 ]
K07763 MMP14; matrix metalloproteinase-14 (membrane-inserted) [EC:3.4.24.80 ]
K07994 MMP13; matrix metalloproteinase-13 (collagenase 3) [EC:3.4.24.-]
K07995 MMP15; matrix metalloproteinase-15 (membrane-inserted) [EC:3.4.24.-]
K07996 MMP16; matrix metalloproteinase-16 (membrane-inserted) [EC:3.4.24.-]
K07997 MMP17; matrix metalloproteinase-17 (membrane-inserted) [EC:3.4.24.-]
K08002 MMP24; matrix metalloproteinase-24 (membrane-inserted) [EC:3.4.24.-]
K08003 MMP25; matrix metalloproteinase-25 (membrane-inserted) [EC:3.4.24.-]
K08523 HBEGF; heparin-binding EGF-like growth factor
K08524 RXRA, NR2B1; retinoid X receptor alpha
K08525 RXRB, NR2B2; retinoid X receptor beta
K08526 RXRG, NR2B3; retinoid X receptor gamma
K08539 VDR, NR1I1; vitamin D3 receptor
K08558 NR4A2, NURR1; nuclear receptor subfamily 4 group A member 2
K08835 OXSR1, STK39; serine/threonine-protein kinase OSR1/STK39 [EC:2.7.11.1 ]
K08845 ARAF, ARAF1; A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K09036 MAFB; transcription factor MAFB
K09047 CREB5, CREBPA; cyclic AMP-responsive element-binding protein 5
K09048 CREB3; cyclic AMP-responsive element-binding protein 3
K09049 ATF6B, CREBL1; cyclic AMP-dependent transcription factor ATF-6 beta
K09203 EGR1; early growth response protein 1
K09260 MEF2A; MADS-box transcription enhancer factor 2A
K09262 MEF2D; MADS-box transcription enhancer factor 2D
K09278 RUNX2, AML3; runt-related transcription factor 2
K12330 ARHGEF1; Rho guanine nucleotide exchange factor 1
K12331 ARHGEF11; Rho guanine nucleotide exchange factor 11
K13365 SLC9A3R1, NHERF1; sodium/hydrogen exchange regulatory cofactor NHE-RF1
K14426 SLC12A3, TSC; solute carrier family 12 (sodium/chloride transporter), member 3
K14683 SLC34A, NPT, nptA; solute carrier family 34 (sodium-dependent phosphate cotransporter)
K16529 ARHGEF13; A-kinase anchor protein 13
K17895 GATA3; GATA-binding protein 3
K21598 GCM; chorion-specific transcription factor GCM
K22428 FGF23; fibroblast growth factor 23
K22608 PTHLH, PTHRP; parathyroid hormone-related hormone
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference Authors Khundmiri SJ, Murray RD, Lederer E
Title PTH and Vitamin D.
Journal Reference Authors Bastepe M, Turan S, He Q
Title Heterotrimeric G proteins in the control of parathyroid hormone actions.
Journal 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 Reference Authors Naveh-Many T, Silver J
Title Transcription factors that determine parathyroid development power PTH expression.
Journal 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 Reference Authors Ferre S, Hoenderop JG, Bindels RJ
Title Sensing mechanisms involved in Ca2+ and Mg2+ homeostasis.
Journal Reference Authors Komaba H, Fukagawa M
Title FGF23-parathyroid interaction: implications in chronic kidney disease.
Journal Reference Authors Bilezikian JP, Cusano NE, Khan AA, Liu JM, Marcocci C, Bandeira F
Title Primary hyperparathyroidism.
Journal 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 Reference Authors Hernando N, Wagner C, Biber J, Murer H
Title Kidney kinase network regulates renal ion cotransport.
Journal 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 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 Reference Authors Zierold C, Mings JA, DeLuca HF
Title Parathyroid hormone regulates 25-hydroxyvitamin D(3)-24-hydroxylase mRNA by altering its stability.
Journal Reference Authors Kramer I, Keller H, Leupin O, Kneissel M
Title Does osteocytic SOST suppression mediate PTH bone anabolism?
Journal 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 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 Reference Authors Pellicelli M, Hariri H, Miller JA, St-Arnaud R
Title Lrp6 is a target of the PTH-activated alphaNAC transcriptional coregulator.
Journal 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 Reference Authors O'Brien CA
Title Control of RANKL gene expression.
Journal Reference Authors Jilka RL
Title Molecular and cellular mechanisms of the anabolic effect of intermittent PTH.
Journal Reference 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 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 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 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 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 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 Reference Authors Agoro R, Ni P, Noonan ML, White KE
Title Osteocytic FGF23 and Its Kidney Function.
Journal Reference Authors Erben RG, Andrukhova O
Title FGF23-Klotho signaling axis in the kidney.
Journal 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 Related ko04961 Endocrine and other factor-regulated calcium reabsorption
