KEGG   PATHWAY: tup04921
Entry
tup04921                    Pathway                                
Name
Oxytocin signaling pathway - Tupaia chinensis (Chinese tree shrew)
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
Pathway map
tup04921  Oxytocin signaling pathway
tup04921

Organism
Tupaia chinensis (Chinese tree shrew) [GN:tup]
Gene
106733328  oxytocin-neurophysin 1-like [KO:K05243]
102502491  oxytocin-neurophysin 1 [KO:K05243]
102502061  OXT; oxytocin/neurophysin I prepropeptide [KO:K05243]
102486567  oxytocin-neurophysin 1-like [KO:K05243]
102481416  OXTR; oxytocin receptor [KO:K04229]
102468263  GNAQ; G protein subunit alpha q [KO:K04634]
102493230  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102500069  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102496534  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
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]
102483700  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
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]
102473333  PLA2G4C; phospholipase A2 group IVC [KO:K16342] [EC:3.1.1.4]
102470223  PLA2G4E; phospholipase A2 group IVE [KO:K16342] [EC:3.1.1.4]
102471767  PLA2G4D; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]
102472618  JMJD7; jmjC domain-containing protein 7 [KO:K16342] [EC:3.1.1.4]
102470647  PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
102477396  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
102478264  PTGS2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]
102469877  MAP2K5; mitogen-activated protein kinase kinase 5 [KO:K04463] [EC:2.7.12.2]
102475335  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
102496870  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
102491199  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
102499043  MEF2C; myocyte enhancer factor 2C [KO:K04454]
102490651  CCND1; cyclin D1 [KO:K04503]
102494763  ELK1; ELK1, ETS transcription factor [KO:K04375]
102475336  RYR1; ryanodine receptor 1 [KO:K04961]
102473653  RYR2; ryanodine receptor 2 [KO:K04962]
102495495  ryanodine receptor 3 [KO:K04963]
102480083  CD38; CD38 molecule [KO:K01242] [EC:3.2.2.6 2.4.99.20]
102485911  TRPM2; transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
102498964  KCNJ2; potassium voltage-gated channel subfamily J member 2 [KO:K04996]
102498995  KCNJ12; potassium voltage-gated channel subfamily J member 12 [KO:K05005]
102492861  KCNJ4; potassium voltage-gated channel subfamily J member 4 [KO:K04998]
102479236  KCNJ14; potassium voltage-gated channel subfamily J member 14 [KO:K05007]
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]
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]
102470788  EEF2K; eukaryotic elongation factor 2 kinase [KO:K08292] [EC:2.7.11.20]
102473867  EEF2; eukaryotic translation elongation factor 2 [KO:K03234]
102484770  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
102482779  CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
102481015  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
102475272  CACNB1; calcium voltage-gated channel auxiliary subunit beta 1 [KO:K04862]
102473215  CACNB2; calcium voltage-gated channel auxiliary subunit beta 2 [KO:K04863]
102502262  CACNB3; calcium voltage-gated channel auxiliary subunit beta 3 [KO:K04864]
102474154  CACNB4; calcium voltage-gated channel auxiliary subunit beta 4 [KO:K04865]
102482417  CACNA2D1; calcium voltage-gated channel auxiliary subunit alpha2delta 1 [KO:K04858]
102494398  CACNA2D2; calcium voltage-gated channel auxiliary subunit alpha2delta 2 [KO:K04859]
102489976  CACNA2D3; calcium voltage-gated channel auxiliary subunit alpha2delta 3 [KO:K04860]
102472656  CACNA2D4; calcium voltage-gated channel auxiliary subunit alpha2delta 4 [KO:K04861]
102496795  CACNG1; calcium voltage-gated channel auxiliary subunit gamma 1 [KO:K04866]
102495760  CACNG2; calcium voltage-gated channel auxiliary subunit gamma 2 [KO:K04867]
102493923  CACNG3; calcium voltage-gated channel auxiliary subunit gamma 3 [KO:K04868]
102489456  CACNG4; calcium voltage-gated channel auxiliary subunit gamma 4 [KO:K04869]
102496364  CACNG5; calcium voltage-gated channel auxiliary subunit gamma 5 [KO:K04870]
102483172  CACNG6; calcium voltage-gated channel auxiliary subunit gamma 6 [KO:K04871]
102482749  CACNG7; calcium voltage-gated channel auxiliary subunit gamma 7 [KO:K04872]
102497622  CACNG8; calcium voltage-gated channel auxiliary subunit gamma 8 [KO:K04873]
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]
102493041  CALM3; calmodulin 3 [KO:K02183]
102484707  neo-calmodulin-like [KO:K02183]
102479773  CALML5; calmodulin like 5 [KO:K02183]
102475973  CALML3; calmodulin-like protein 3 [KO:K02183]
102485493  calmodulin-like [KO:K02183]
102472462  CALM1; calmodulin 1 [KO:K02183]
102493190  CALM2; calmodulin 2 [KO:K02183]
102468681  CALML6; calmodulin like 6 [KO:K02183]
102495258  CALMODULIN; calmodulin-alpha [KO:K02183]
102483795  CALML4; calmodulin like 4 [KO:K02183]
102480885  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
102478870  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
102478627  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
102478386  PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
102474096  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
102481120  NFATC1; nuclear factor of activated T-cells 1 [KO:K04446]
102478659  NFATC2; nuclear factor of activated T-cells 2 [KO:K17332]
102498127  NFATC3; nuclear factor of activated T-cells 3 [KO:K17333]
102468121  NFATC4; nuclear factor of activated T-cells 4 [KO:K17334]
102501927  regulator of G-protein signaling 2 [KO:K18154]
102492666  regulator of G-protein signaling 2 [KO:K18154]
102494917  RCAN1; regulator of calcineurin 1 [KO:K17901]
102493235  CAMKK2; calcium/calmodulin dependent protein kinase kinase 2 [KO:K07359] [EC:2.7.11.17]
102491119  PRKAA2; protein kinase AMP-activated catalytic subunit alpha 2 [KO:K07198] [EC:2.7.11.31]
106735707  PRKAA1; protein kinase AMP-activated catalytic subunit alpha 1 [KO:K07198] [EC:2.7.11.31]
102477154  PRKAB2; protein kinase AMP-activated non-catalytic subunit beta 2 [KO:K07199]
102471560  PRKAB1; protein kinase AMP-activated non-catalytic subunit beta 1 [KO:K07199]
102502947  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200]
102471857  PRKAG3; protein kinase AMP-activated non-catalytic subunit gamma 3 [KO:K07200]
102498498  PRKAG1; protein kinase AMP-activated non-catalytic subunit gamma 1 [KO:K07200]
102478578  CAMK1D; calcium/calmodulin dependent protein kinase ID [KO:K08794] [EC:2.7.11.17]
102473558  CAMK1; calcium/calmodulin dependent protein kinase I [KO:K08794] [EC:2.7.11.17]
102500231  CAMK1G; calcium/calmodulin dependent protein kinase IG [KO:K08794] [EC:2.7.11.17]
102494625  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
102482912  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
102472689  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
102503259  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
102479520  CAMK4; calcium/calmodulin dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
102495986  NOS3; nitric oxide synthase 3 [KO:K13242] [EC:1.14.13.39]
102469297  GUCY1A2; guanylate cyclase 1 soluble subunit alpha 2 [KO:K12318] [EC:4.6.1.2]
102483882  GUCY1A3; guanylate cyclase 1 soluble subunit alpha [KO:K12318] [EC:4.6.1.2]
102485635  guanylate cyclase soluble subunit beta-2 [KO:K12319] [EC:4.6.1.2]
102488370  GUCY1B3; guanylate cyclase 1 soluble subunit beta [KO:K12319] [EC:4.6.1.2]
102476150  NPPA; natriuretic peptide A [KO:K12334]
102482734  NPR1; natriuretic peptide receptor 1 [KO:K12323] [EC:4.6.1.2]
102502023  NPR2; natriuretic peptide receptor 2 [KO:K12324] [EC:4.6.1.2]
102498032  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
102476504  MYLK; myosin light chain kinase [KO:K00907] [EC:2.7.11.18]
102489117  MYLK2; myosin light chain kinase 2 [KO:K00907] [EC:2.7.11.18]
102468205  MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
102471120  MYL6B; myosin light chain 6B [KO:K12751]
102471830  MYL6; myosin light chain 6 [KO:K12751]
102483320  MYL9; myosin light chain 9 [KO:K12755]
102479926  ACTB; actin beta [KO:K05692]
102498431  ACTG1; actin gamma 1 [KO:K05692]
102487039  RHOA; ras homolog family member A [KO:K04513]
102481136  ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.39]
102490242  ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.39]
102476316  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
102496931  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
102469176  serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
102477186  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
102473894  PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
102500634  PPP1R12B; protein phosphatase 1 regulatory subunit 12B [KO:K12329]
102475906  PPP1R12C; protein phosphatase 1 regulatory subunit 12C [KO:K17457]
102489563  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
102501321  neuroendocrine secretory protein 55 [KO:K04632]
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]
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]
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]
102483059  GNAO1; G protein subunit alpha o1 [KO:K04534]
102472442  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
102470324  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
102485065  PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290]
102491807  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
102500280  KCNJ3; potassium voltage-gated channel subfamily J member 3 [KO:K04997]
102502044  KCNJ6; potassium voltage-gated channel subfamily J member 6 [KO:K05000]
102484768  KCNJ9; potassium voltage-gated channel subfamily J member 9 [KO:K05002]
102482239  KCNJ5; potassium voltage-gated channel subfamily J member 5 [KO:K04999]
102485304  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102490159  CDKN1A; cyclin dependent kinase inhibitor 1A [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
Reference
PMID:18655881
  Authors
Devost D, Wrzal P, Zingg HH
  Title
Oxytocin receptor signalling.
  Journal
Prog Brain Res 170:167-76 (2008)
DOI:10.1016/S0079-6123(08)00415-9
Reference
PMID:20626426
  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)
DOI:10.1111/j.1755-5949.2010.00185.x
Reference
PMID:21981277
  Authors
Gutkowska J, Jankowski M
  Title
Oxytocin revisited: its role in cardiovascular regulation.
  Journal
J Neuroendocrinol 24:599-608 (2012)
DOI:10.1111/j.1365-2826.2011.02235.x
Reference
PMID:22190926
  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)
DOI:10.1155/2011/350546
Reference
PMID:19840865
  Authors
Tom N, Assinder SJ
  Title
Oxytocin in health and disease.
  Journal
Int J Biochem Cell Biol 42:202-5 (2010)
DOI:10.1016/j.biocel.2009.10.008
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)
DOI:10.1152/ajpendo.1998.274.4.E634
Reference
PMID:12009385
  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
PMID:16787565
  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)
DOI:10.1111/j.1745-7254.2006.00393.x
Reference
PMID:11861513
  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)
DOI:10.1210/endo.143.3.8696
Reference
PMID:12433531
  Authors
Slattery MM, Morrison JJ
  Title
Preterm delivery.
  Journal
Lancet 360:1489-97 (2002)
DOI:10.1016/S0140-6736(02)11476-0
Reference
PMID:22902539
  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)
DOI:10.1210/me.2012-1057
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)
DOI:10.1073/pnas.94.21.11704
Reference
PMID:14715914
  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)
DOI:10.1152/physrev.00017.2003
Reference
PMID:18555543
  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)
DOI:10.1016/j.regpep.2008.05.001
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)
DOI:10.1002/(SICI)1097-0215(19970717)72:2<340::AID-IJC23>3.0.CO;2-I
Reference
PMID:23356278
  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)
DOI:10.1042/BST20120306
Reference
PMID:16966388
  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)
DOI:10.1152/ajpregu.00333.2006
Reference
PMID:20141572
  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)
DOI:10.1111/j.1365-2826.2010.01970.x
Reference
PMID:22227279
  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)
DOI:10.1016/j.yhbeh.2011.12.011
Reference
PMID:23335873
  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)
DOI:10.3389/fnins.2012.00182
Reference
PMID:16156781
  Authors
Guse AH
  Title
Second messenger function and the structure-activity relationship of cyclic adenosine diphosphoribose (cADPR).
  Journal
FEBS J 272:4590-7 (2005)
DOI:10.1111/j.1742-4658.2005.04863.x
Related
pathway
tup00590  Arachidonic acid metabolism
tup04010  MAPK signaling pathway
tup04020  Calcium signaling pathway
tup04110  Cell cycle
KO pathway
ko04921   
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