KEGG   PATHWAY: hsa04921Help
Entry
hsa04921                    Pathway                                

Name
Oxytocin signaling pathway - Homo sapiens (human)
Description
Oxytocin (OT) is a nonapeptide synthesized by the magno-cellular neurons located in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus. It exerts a wide variety of central and peripheral effects.  However, its best-known and most well-established roles are stimulation of uterine contractions during parturition and milk release during lactation. Oxytocin also influences cardiovascular regulation and various social behaviors. The actions of OT are all mediated by one type of OT receptor (OTR). This is a transmembrane receptor belonging to the G-protein-coupled receptor superfamily. The main signaling pathway is the Gq/PLC/Ins3 pathway, but the MAPK and the RhoA/Rho kinase pathways are also activated, contributing to increased prostaglandin production and direct contractile effect on myometrial cells. In the cardiovascular system, OTR is associated with the ANP-cGMP and NO-cGMP pathways, which reduce the force and rate of contraction and increase vasodilatation.
Class
Organismal Systems; Endocrine system
BRITE hierarchy
Pathway map
Oxytocin signaling pathway
hsa04921

All organismsOrtholog table
Organism
Homo sapiens (human) [GN:hsa]
Gene
5020  
OXT; oxytocin/neurophysin I prepropeptide [KO:K05243]
5021  
OXTR; oxytocin receptor [KO:K04229]
2776  
GNAQ; guanine nucleotide binding protein (G protein), q polypeptide [KO:K04634]
3265  
HRAS; Harvey rat sarcoma viral oncogene homolog [KO:K02833]
3845  
KRAS; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
4893  
NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [KO:K07828]
5894  
RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
5604  
MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  
MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
123745  
PLA2G4E; phospholipase A2, group IVE [KO:K16342] [EC:3.1.1.4]
5321  
PLA2G4A; phospholipase A2, group IVA (cytosolic, calcium-dependent) [KO:K16342] [EC:3.1.1.4]
8681  
JMJD7-PLA2G4B; JMJD7-PLA2G4B readthrough [KO:K16342] [EC:3.1.1.4]
PLA2G4B; phospholipase A2, group IVB (cytosolic) [KO:K16342] [EC:3.1.1.4]
8605  
PLA2G4C; phospholipase A2, group IVC (cytosolic, calcium-independent) [KO:K16342] [EC:3.1.1.4]
283748  
PLA2G4D; phospholipase A2, group IVD (cytosolic) [KO:K16342] [EC:3.1.1.4]
255189  
PLA2G4F; phospholipase A2, group IVF [KO:K16342] [EC:3.1.1.4]
5743  
PTGS2; prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) [KO:K11987] [EC:1.14.99.1]
5607  
MAP2K5; mitogen-activated protein kinase kinase 5 [KO:K04463] [EC:2.7.12.2]
5598  
MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
3725  
JUN; jun proto-oncogene [KO:K04448]
2353  
FOS; FBJ murine osteosarcoma viral oncogene homolog [KO:K04379]
4208  
MEF2C; myocyte enhancer factor 2C [KO:K04454]
595  
CCND1; cyclin D1 [KO:K04503]
2002  
ELK1; ELK1, member of ETS oncogene family [KO:K04375]
6261  
RYR1; ryanodine receptor 1 (skeletal) [KO:K04961]
6262  
RYR2; ryanodine receptor 2 (cardiac) [KO:K04962]
6263  
RYR3; ryanodine receptor 3 [KO:K04963]
952  
CD38; CD38 molecule [KO:K01242] [EC:2.4.99.20 3.2.2.6]
7226  
TRPM2; transient receptor potential cation channel, subfamily M, member 2 [KO:K04977]
3759  
KCNJ2; potassium inwardly-rectifying channel, subfamily J, member 2 [KO:K04996]
3768  
KCNJ12; potassium inwardly-rectifying channel, subfamily J, member 12 [KO:K05005]
3761  
KCNJ4; potassium inwardly-rectifying channel, subfamily J, member 4 [KO:K04998]
3770  
KCNJ14; potassium inwardly-rectifying channel, subfamily J, member 14 [KO:K05007]
23236  
PLCB1; phospholipase C, beta 1 (phosphoinositide-specific) [KO:K05858] [EC:3.1.4.11]
5330  
PLCB2; phospholipase C, beta 2 [KO:K05858] [EC:3.1.4.11]
5331  
PLCB3; phospholipase C, beta 3 (phosphatidylinositol-specific) [KO:K05858] [EC:3.1.4.11]
5332  
PLCB4; phospholipase C, beta 4 [KO:K05858] [EC:3.1.4.11]
5578  
PRKCA; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
5579  
PRKCB; protein kinase C, beta [KO:K02677] [EC:2.7.11.13]
5582  
PRKCG; protein kinase C, gamma [KO:K02677] [EC:2.7.11.13]
29904  
EEF2K; eukaryotic elongation factor-2 kinase [KO:K08292] [EC:2.7.11.20]
eukaryotic elongation factor 2 kinase-like; K08292 elongation factor 2 kinase [EC:2.7.11.20] [KO:K08292] [EC:2.7.11.20]
1938  
EEF2; eukaryotic translation elongation factor 2 [KO:K03234]
775  
CACNA1C; calcium channel, voltage-dependent, L type, alpha 1C subunit [KO:K04850]
776  
CACNA1D; calcium channel, voltage-dependent, L type, alpha 1D subunit [KO:K04851]
778  
CACNA1F; calcium channel, voltage-dependent, L type, alpha 1F subunit [KO:K04853]
779  
CACNA1S; calcium channel, voltage-dependent, L type, alpha 1S subunit [KO:K04857]
782  
CACNB1; calcium channel, voltage-dependent, beta 1 subunit [KO:K04862]
783  
CACNB2; calcium channel, voltage-dependent, beta 2 subunit [KO:K04863]
784  
CACNB3; calcium channel, voltage-dependent, beta 3 subunit [KO:K04864]
785  
CACNB4; calcium channel, voltage-dependent, beta 4 subunit [KO:K04865]
781  
CACNA2D1; calcium channel, voltage-dependent, alpha 2/delta subunit 1 [KO:K04858]
9254  
CACNA2D2; calcium channel, voltage-dependent, alpha 2/delta subunit 2 [KO:K04859]
55799  
CACNA2D3; calcium channel, voltage-dependent, alpha 2/delta subunit 3 [KO:K04860]
93589  
CACNA2D4; calcium channel, voltage-dependent, alpha 2/delta subunit 4 [KO:K04861]
786  
CACNG1; calcium channel, voltage-dependent, gamma subunit 1 [KO:K04866]
10369  
CACNG2; calcium channel, voltage-dependent, gamma subunit 2 [KO:K04867]
10368  
CACNG3; calcium channel, voltage-dependent, gamma subunit 3 [KO:K04868]
27092  
CACNG4; calcium channel, voltage-dependent, gamma subunit 4 [KO:K04869]
27091  
CACNG5; calcium channel, voltage-dependent, gamma subunit 5 [KO:K04870]
59285  
CACNG6; calcium channel, voltage-dependent, gamma subunit 6 [KO:K04871]
59284  
CACNG7; calcium channel, voltage-dependent, gamma subunit 7 [KO:K04872]
59283  
CACNG8; calcium channel, voltage-dependent, gamma subunit 8 [KO:K04873]
3708  
ITPR1; inositol 1,4,5-trisphosphate receptor, type 1 [KO:K04958]
3709  
ITPR2; inositol 1,4,5-trisphosphate receptor, type 2 [KO:K04959]
3710  
ITPR3; inositol 1,4,5-trisphosphate receptor, type 3 [KO:K04960]
810  
CALML3; calmodulin-like 3 [KO:K02183]
805  
CALM2; calmodulin 2 (phosphorylase kinase, delta) [KO:K02183]
808  
CALM3; calmodulin 3 (phosphorylase kinase, delta) [KO:K02183]
801  
CALM1; calmodulin 1 (phosphorylase kinase, delta) [KO:K02183]
163688  
CALML6; calmodulin-like 6 [KO:K02183]
51806  
CALML5; calmodulin-like 5 [KO:K02183]
5530  
PPP3CA; protein phosphatase 3, catalytic subunit, alpha isozyme [KO:K04348] [EC:3.1.3.16]
5532  
PPP3CB; protein phosphatase 3, catalytic subunit, beta isozyme [KO:K04348] [EC:3.1.3.16]
5533  
PPP3CC; protein phosphatase 3, catalytic subunit, gamma isozyme [KO:K04348] [EC:3.1.3.16]
5534  
PPP3R1; protein phosphatase 3, regulatory subunit B, alpha [KO:K06268]
5535  
PPP3R2; protein phosphatase 3, regulatory subunit B, beta [KO:K06268]
4772  
NFATC1; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 [KO:K04446]
4773  
NFATC2; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2 [KO:K17332]
4775  
NFATC3; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3 [KO:K17333]
4776  
NFATC4; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4 [KO:K17334]
5997  
RGS2; regulator of G-protein signaling 2 [KO:K18154]
1827  
RCAN1; regulator of calcineurin 1 [KO:K17901]
84254  
CAMKK1; calcium/calmodulin-dependent protein kinase kinase 1, alpha [KO:K07359] [EC:2.7.11.17]
10645  
CAMKK2; calcium/calmodulin-dependent protein kinase kinase 2, beta [KO:K07359] [EC:2.7.11.17]
5562  
PRKAA1; protein kinase, AMP-activated, alpha 1 catalytic subunit [KO:K07198] [EC:2.7.11.11]
5563  
PRKAA2; protein kinase, AMP-activated, alpha 2 catalytic subunit [KO:K07198] [EC:2.7.11.11]
5564  
PRKAB1; protein kinase, AMP-activated, beta 1 non-catalytic subunit [KO:K07199]
5565  
PRKAB2; protein kinase, AMP-activated, beta 2 non-catalytic subunit [KO:K07199]
5571  
PRKAG1; protein kinase, AMP-activated, gamma 1 non-catalytic subunit [KO:K07200]
53632  
PRKAG3; protein kinase, AMP-activated, gamma 3 non-catalytic subunit [KO:K07200]
51422  
PRKAG2; protein kinase, AMP-activated, gamma 2 non-catalytic subunit [KO:K07200]
57118  
CAMK1D; calcium/calmodulin-dependent protein kinase ID [KO:K08794] [EC:2.7.11.17]
57172  
CAMK1G; calcium/calmodulin-dependent protein kinase IG [KO:K08794] [EC:2.7.11.17]
8536  
CAMK1; calcium/calmodulin-dependent protein kinase I [KO:K08794] [EC:2.7.11.17]
815  
CAMK2A; calcium/calmodulin-dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
817  
CAMK2D; calcium/calmodulin-dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
816  
CAMK2B; calcium/calmodulin-dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
818  
CAMK2G; calcium/calmodulin-dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
814  
CAMK4; calcium/calmodulin-dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
4846  
NOS3; nitric oxide synthase 3 (endothelial cell) [KO:K13242] [EC:1.14.13.39]
2977  
GUCY1A2; guanylate cyclase 1, soluble, alpha 2 [KO:K12318] [EC:4.6.1.2]
2982  
GUCY1A3; guanylate cyclase 1, soluble, alpha 3 [KO:K12318] [EC:4.6.1.2]
2983  
GUCY1B3; guanylate cyclase 1, soluble, beta 3 [KO:K12319] [EC:4.6.1.2]
4881  
NPR1; natriuretic peptide receptor 1 [KO:K12323] [EC:4.6.1.2]
4882  
NPR2; natriuretic peptide receptor 2 [KO:K12324] [EC:4.6.1.2]
4638  
MYLK; myosin light chain kinase [KO:K00907] [EC:2.7.11.18]
85366  
MYLK2; myosin light chain kinase 2 [KO:K00907] [EC:2.7.11.18]
91807  
MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
340156  
MYLK4; myosin light chain kinase family, member 4 [KO:K00907] [EC:2.7.11.18]
140465  
MYL6B; myosin, light chain 6B, alkali, smooth muscle and non-muscle [KO:K12751]
4637  
MYL6; myosin, light chain 6, alkali, smooth muscle and non-muscle [KO:K12751]
10398  
MYL9; myosin, light chain 9, regulatory [KO:K12755]
60  
ACTB; actin, beta [KO:K05692]
71  
ACTG1; actin, gamma 1 [KO:K05692]
387  
RHOA; ras homolog family member A [KO:K04513]
6093  
ROCK1; Rho-associated, coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.1]
9475  
ROCK2; Rho-associated, coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.1]
5499  
PPP1CA; protein phosphatase 1, catalytic subunit, alpha isozyme [KO:K06269] [EC:3.1.3.16]
5500  
PPP1CB; protein phosphatase 1, catalytic subunit, beta isozyme [KO:K06269] [EC:3.1.3.16]
5501  
PPP1CC; protein phosphatase 1, catalytic subunit, gamma isozyme [KO:K06269] [EC:3.1.3.16]
4659  
PPP1R12A; protein phosphatase 1, regulatory subunit 12A [KO:K06270]
4660  
PPP1R12B; protein phosphatase 1, regulatory subunit 12B [KO:K12329]
54776  
PPP1R12C; protein phosphatase 1, regulatory subunit 12C [KO:K17457]
2778  
GNAS; GNAS complex locus [KO:K04632]
107  
ADCY1; adenylate cyclase 1 (brain) [KO:K08041] [EC:4.6.1.1]
108  
ADCY2; adenylate cyclase 2 (brain) [KO:K08042] [EC:4.6.1.1]
109  
ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
196883  
ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
111  
ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
112  
ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
113  
ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
114  
ADCY8; adenylate cyclase 8 (brain) [KO:K08048] [EC:4.6.1.1]
115  
ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
5566  
PRKACA; protein kinase, cAMP-dependent, catalytic, alpha [KO:K04345] [EC:2.7.11.11]
5567  
PRKACB; protein kinase, cAMP-dependent, catalytic, beta [KO:K04345] [EC:2.7.11.11]
5568  
PRKACG; protein kinase, cAMP-dependent, catalytic, gamma [KO:K04345] [EC:2.7.11.11]
5613  
PRKX; protein kinase, X-linked [KO:K04345] [EC:2.7.11.11]
2770  
GNAI1; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1 [KO:K04630]
2773  
GNAI3; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 3 [KO:K04630]
2771  
GNAI2; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2 [KO:K04630]
2775  
GNAO1; guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O [KO:K04534]
5290  
PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  
PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  
PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5294  
PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
5295  
PIK3R1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
23533  
PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
5296  
PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
8503  
PIK3R3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [KO:K02649]
6714  
SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
3760  
KCNJ3; potassium inwardly-rectifying channel, subfamily J, member 3 [KO:K04997]
3763  
KCNJ6; potassium inwardly-rectifying channel, subfamily J, member 6 [KO:K05000]
3765  
KCNJ9; potassium inwardly-rectifying channel, subfamily J, member 9 [KO:K05002]
3762  
KCNJ5; potassium inwardly-rectifying channel, subfamily J, member 5 [KO:K04999]
1956  
EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
1026  
CDKN1A; cyclin-dependent kinase inhibitor 1A (p21, Cip1) [KO:K06625]
Compound
C00076  
Calcium cation
C00165  
Diacylglycerol
C00219  
Arachidonate
C00238  
Potassium cation
C00427  
Prostaglandin H2
C00533  
Nitric oxide
C00575  
3',5'-Cyclic AMP
C00584  
Prostaglandin E2
C00639  
Prostaglandin F2alpha
C00942  
3',5'-Cyclic GMP
C01245  
D-myo-Inositol 1,4,5-trisphosphate
C13050  
Cyclic ADP-ribose
C16003  
Atrial natriuretic peptide
Reference
  Authors
Devost D, Wrzal P, Zingg HH
  Title
Oxytocin receptor signalling.
  Journal
Prog Brain Res 170:167-76 (2008)
Reference
  Authors
Viero C, Shibuya I, Kitamura N, Verkhratsky A, Fujihara H, Katoh A, Ueta Y, Zingg HH, Chvatal A, Sykova E, Dayanithi G
  Title
REVIEW: Oxytocin: Crossing the bridge between basic science and pharmacotherapy.
  Journal
CNS Neurosci Ther 16:e138-56 (2010)
Reference
  Authors
Gutkowska J, Jankowski M
  Title
Oxytocin revisited: its role in cardiovascular regulation.
  Journal
J Neuroendocrinol 24:599-608 (2012)
Reference
  Authors
Vrachnis N, Malamas FM, Sifakis S, Deligeoroglou E, Iliodromiti Z
  Title
The oxytocin-oxytocin receptor system and its antagonists as tocolytic agents.
  Journal
Int J Endocrinol 2011:350546 (2011)
Reference
  Authors
Tom N, Assinder SJ
  Title
Oxytocin in health and disease.
  Journal
Int J Biochem Cell Biol 42:202-5 (2010)
Reference
PMID:9575824
  Authors
Strakova Z, Copland JA, Lolait SJ, Soloff MS
  Title
ERK2 mediates oxytocin-stimulated PGE2 synthesis.
  Journal
Am J Physiol 274:E634-41 (1998)
Reference
  Authors
Slater DM, Zervou S, Thornton S
  Title
Prostaglandins and prostanoid receptors in human pregnancy and parturition.
  Journal
J Soc Gynecol Investig 9:118-24 (2002)
Reference
  Authors
Shmygol A, Gullam J, Blanks A, Thornton S
  Title
Multiple mechanisms involved in oxytocin-induced modulation of myometrial contractility.
  Journal
Acta Pharmacol Sin 27:827-32 (2006)
Reference
  Authors
Tahara M, Morishige K, Sawada K, Ikebuchi Y, Kawagishi R, Tasaka K, Murata Y
  Title
RhoA/Rho-kinase cascade is involved in oxytocin-induced rat uterine contraction.
  Journal
Endocrinology 143:920-9 (2002)
Reference
  Authors
Slattery MM, Morrison JJ
  Title
Preterm delivery.
  Journal
Lancet 360:1489-97 (2002)
Reference
  Authors
Pont JN, McArdle CA, Lopez Bernal A
  Title
Oxytocin-stimulated NFAT transcriptional activation in human myometrial cells.
  Journal
Mol Endocrinol 26:1743-56 (2012)
Reference
PMID:9326674
  Authors
Gutkowska J, Jankowski M, Lambert C, Mukaddam-Daher S, Zingg HH, McCann SM
  Title
Oxytocin releases atrial natriuretic peptide by combining with oxytocin receptors in the heart.
  Journal
Proc Natl Acad Sci U S A 94:11704-9 (1997)
Reference
  Authors
Antunes-Rodrigues J, de Castro M, Elias LL, Valenca MM, McCann SM
  Title
Neuroendocrine control of body fluid metabolism.
  Journal
Physiol Rev 84:169-208 (2004)
Reference
  Authors
Lee ES, Uhm KO, Lee YM, Kwon J, Park SH, Soo KH
  Title
Oxytocin stimulates glucose uptake in skeletal muscle cells through the calcium-CaMKK-AMPK pathway.
  Journal
Regul Pept 151:71-4 (2008)
Reference
PMID:9219843
  Authors
Cassoni P, Sapino A, Fortunati N, Munaron L, Chini B, Bussolati G
  Title
Oxytocin inhibits the proliferation of MDA-MB231 human breast-cancer cells via cyclic adenosine monophosphate and protein kinase A.
  Journal
Int J Cancer 72:340-4 (1997)
Reference
  Authors
Busnelli M, Peverelli E, Mantovani G, Spada A, Chini B
  Title
Deciphering the specific role of G(alphai/o) isoforms: functional selective oxytocin ligands and somatostatin SST5 receptor mutants.
  Journal
Biochem Soc Trans 41:166-71 (2013)
Reference
  Authors
Reversi A, Rimoldi V, Brambillasca S, Chini B
  Title
Effects of cholesterol manipulation on the signaling of the human oxytocin receptor.
  Journal
Am J Physiol Regul Integr Comp Physiol 291:R861-9 (2006)
Reference
  Authors
Salmina AB, Lopatina O, Ekimova MV, Mikhutkina SV, Higashida H
  Title
CD38/cyclic ADP-ribose system: a new player for oxytocin secretion and regulation of social behaviour.
  Journal
J Neuroendocrinol 22:380-92 (2010)
Reference
  Authors
Higashida H, Yokoyama S, Kikuchi M, Munesue T
  Title
CD38 and its role in oxytocin secretion and social behavior.
  Journal
Horm Behav 61:351-8 (2012)
Reference
  Authors
Lopatina O, Inzhutova A, Salmina AB, Higashida H
  Title
The roles of oxytocin and CD38 in social or parental behaviors.
  Journal
Front Neurosci 6:182 (2012)
Reference
  Authors
Guse AH
  Title
Second messenger function and the structure-activity relationship of cyclic adenosine diphosphoribose (cADPR).
  Journal
FEBS J 272:4590-7 (2005)
KO pathway
 

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