KEGG   PATHWAY: bom04921
Entry
bom04921                    Pathway                                
Name
Oxytocin signaling pathway - Bos mutus (wild yak)
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
bom04921  Oxytocin signaling pathway
bom04921

Organism
Bos mutus (wild yak) [GN:bom]
Gene
102272042  OXTR; oxytocin receptor [KO:K04229]
102287414  GNAQ; G protein subunit alpha q [KO:K04634]
102278591  GTPase HRas [KO:K02833]
102277011  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102286500  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102269203  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102288216  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102280670  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102271710  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102272368  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102284931  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102271639  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
102282019  PLA2G4B; phospholipase A2 group IVB [KO:K16342] [EC:3.1.1.4]
102282862  PLA2G4D; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]
102283142  PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
102282579  PLA2G4E; phospholipase A2 group IVE [KO:K16342] [EC:3.1.1.4]
102271174  PTGS2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]
102283668  MAP2K5; mitogen-activated protein kinase kinase 5 [KO:K04463] [EC:2.7.12.2]
102278560  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
102267895  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
102275053  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
102286323  MEF2C; myocyte enhancer factor 2C [KO:K04454]
102270546  CCND1; cyclin D1 [KO:K04503]
102286114  ELK1; ELK1, ETS transcription factor [KO:K04375]
102275567  RYR1; ryanodine receptor 1 [KO:K04961]
102280999  RYR2; ryanodine receptor 2 [KO:K04962]
102270854  RYR3; ryanodine receptor 3 [KO:K04963]
102273331  CD38; CD38 molecule [KO:K01242] [EC:3.2.2.6 2.4.99.20]
102268934  TRPM2; transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
102272385  KCNJ2; potassium voltage-gated channel subfamily J member 2 [KO:K04996]
102267497  KCNJ12; potassium voltage-gated channel subfamily J member 12 [KO:K05005]
102287252  KCNJ4; potassium voltage-gated channel subfamily J member 4 [KO:K04998]
102285525  KCNJ14; potassium voltage-gated channel subfamily J member 14 [KO:K05007]
102264989  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
102278948  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
102273347  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
102276260  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
102278724  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
102274116  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
102265831  PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
102283488  EEF2K; eukaryotic elongation factor 2 kinase [KO:K08292] [EC:2.7.11.20]
102271153  EEF2; eukaryotic translation elongation factor 2 [KO:K03234]
102277590  CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
102271623  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
102286805  CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
102272241  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
102287719  CACNB1; calcium voltage-gated channel auxiliary subunit beta 1 [KO:K04862]
102284956  CACNB2; calcium voltage-gated channel auxiliary subunit beta 2 [KO:K04863]
102265606  CACNB3; calcium voltage-gated channel auxiliary subunit beta 3 [KO:K04864]
102265990  CACNB4; calcium voltage-gated channel auxiliary subunit beta 4 [KO:K04865]
102268507  CACNA2D1; calcium voltage-gated channel auxiliary subunit alpha2delta 1 [KO:K04858]
102284671  CACNA2D2; calcium voltage-gated channel auxiliary subunit alpha2delta 2 [KO:K04859]
102269496  CACNA2D3; calcium voltage-gated channel auxiliary subunit alpha2delta 3 [KO:K04860]
102277012  CACNA2D4; calcium voltage-gated channel auxiliary subunit alpha2delta 4 [KO:K04861]
102278998  CACNG1; calcium voltage-gated channel auxiliary subunit gamma 1 [KO:K04866]
102281578  CACNG2; calcium voltage-gated channel auxiliary subunit gamma 2 [KO:K04867]
102273826  CACNG3; calcium voltage-gated channel auxiliary subunit gamma 3 [KO:K04868]
102276480  CACNG5; calcium voltage-gated channel auxiliary subunit gamma 5 [KO:K04870]
102265546  CACNG7; calcium voltage-gated channel auxiliary subunit gamma 7 [KO:K04872]
102266971  uncharacterized LOC102266971 [KO:K04873]
102269088  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102269013  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102271039  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102280361  calmodulin-alpha [KO:K02183]
102285968  CALML6; calmodulin like 6 [KO:K02183]
102281667  CALM1; calmodulin 1 [KO:K02183]
102287375  calmodulin [KO:K02183]
102268061  CALM2; calmodulin 2 [KO:K02183]
102265605  calmodulin-alpha [KO:K02183]
102266295  calmodulin [KO:K02183]
102282476  CALM3; calmodulin 3 [KO:K02183]
102269657  CALML3; calmodulin-like protein 3 [KO:K02183]
102271961  calmodulin-2/4-like [KO:K02183]
102284406  CALML4; calmodulin like 4 [KO:K02183]
102275863  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
102286752  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
102266749  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
102272271  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
102277736  PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
102286049  nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
102285474  nuclear factor of activated T-cells, cytoplasmic 1-like [KO:K04446]
102277605  NFATC2; nuclear factor of activated T-cells 2 [KO:K17332]
102281905  NFATC3; nuclear factor of activated T-cells 3 [KO:K17333]
102285411  NFATC4; nuclear factor of activated T-cells 4 [KO:K17334]
102272005  RGS2; regulator of G-protein signaling 2 [KO:K18154]
102287064  RCAN1; regulator of calcineurin 1 [KO:K17901]
102275357  CAMKK2; calcium/calmodulin dependent protein kinase kinase 2 [KO:K07359] [EC:2.7.11.17]
102270414  PRKAA2; protein kinase AMP-activated catalytic subunit alpha 2 [KO:K07198] [EC:2.7.11.31]
102265959  PRKAA1; protein kinase AMP-activated catalytic subunit alpha 1 [KO:K07198] [EC:2.7.11.31]
102278235  PRKAB1; protein kinase AMP-activated non-catalytic subunit beta 1 [KO:K07199]
102275377  PRKAB2; protein kinase AMP-activated non-catalytic subunit beta 2 [KO:K07199]
102276048  PRKAG3; protein kinase AMP-activated non-catalytic subunit gamma 3 [KO:K07200]
102277941  PRKAG2; protein kinase AMP-activated non-catalytic subunit gamma 2 [KO:K07200]
102268424  PRKAG1; protein kinase AMP-activated non-catalytic subunit gamma 1 [KO:K07200]
102283599  CAMK1D; calcium/calmodulin dependent protein kinase ID [KO:K08794] [EC:2.7.11.17]
102268851  CAMK1; calcium/calmodulin dependent protein kinase I [KO:K08794] [EC:2.7.11.17]
102274680  CAMK1G; calcium/calmodulin dependent protein kinase IG [KO:K08794] [EC:2.7.11.17]
102281822  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
102271451  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
102279381  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
102280002  calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
102264521  CAMK4; calcium/calmodulin dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
102267556  NOS3; nitric oxide synthase 3 [KO:K13242] [EC:1.14.13.39]
102281834  GUCY1A3; guanylate cyclase 1 soluble subunit alpha [KO:K12318] [EC:4.6.1.2]
102280817  GUCY1A2; guanylate cyclase 1 soluble subunit alpha 2 [KO:K12318] [EC:4.6.1.2]
102282106  GUCY1B3; guanylate cyclase 1 soluble subunit beta [KO:K12319] [EC:4.6.1.2]
102285947  guanylate cyclase soluble subunit beta-2-like [KO:K12319] [EC:4.6.1.2]
102287668  NPPA; natriuretic peptide A [KO:K12334]
102279810  NPR1; natriuretic peptide receptor 1 [KO:K12323] [EC:4.6.1.2]
102278070  NPR2; natriuretic peptide receptor 2 [KO:K12324] [EC:4.6.1.2]
102264349  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
102275601  MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
102276600  MYLK2; myosin light chain kinase 2 [KO:K00907] [EC:2.7.11.18]
102269080  MYLK; myosin light chain kinase [KO:K00907] [EC:2.7.11.18]
102275450  MYL6; myosin light chain 6 [KO:K12751]
102275160  MYL6B; myosin light chain 6B [KO:K12751]
102265044  MYL9; myosin light chain 9 [KO:K12755]
102285564  ACTG1; actin gamma 1 [KO:K05692]
102286048  ACTB; actin beta [KO:K05692]
102280554  RHOA; ras homolog family member A [KO:K04513]
102284712  ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.1]
102267122  ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.1]
102270793  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
102275429  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
102266876  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
102268036  PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
102286584  PPP1R12B; protein phosphatase 1 regulatory subunit 12B [KO:K12329]
102273254  PPP1R12C; protein phosphatase 1 regulatory subunit 12C [KO:K17457]
102266153  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
102286123  neuroendocrine secretory protein 55 [KO:K04632]
102267116  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
102274117  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
102282732  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
102286168  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
102276460  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
102265325  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
102266966  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
102272964  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
102285642  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
102281757  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102269124  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
102285228  GNAI3; G protein subunit alpha i3 [KO:K04630]
102274651  GNAI2; G protein subunit alpha i2 [KO:K04630]
102273920  GNAI1; G protein subunit alpha i1 [KO:K04630]
102280695  GNAO1; G protein subunit alpha o1 [KO:K04534]
102277419  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
102282596  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
102279608  PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290]
102284506  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
102269266  KCNJ3; potassium voltage-gated channel subfamily J member 3 [KO:K04997]
102274100  KCNJ6; potassium voltage-gated channel subfamily J member 6 [KO:K05000]
102271283  KCNJ9; potassium voltage-gated channel subfamily J member 9 [KO:K05002]
102266376  KCNJ5; potassium voltage-gated channel subfamily J member 5 [KO:K04999]
102269868  epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102268672  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
bom00590  Arachidonic acid metabolism
bom04010  MAPK signaling pathway
bom04020  Calcium signaling pathway
bom04110  Cell cycle
KO pathway
ko04921   

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Genome (1)   
   KEGG GENOME (1)   
Gene (155)   
   KEGG GENES (155)   
All databases (156)   

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