KEGG   PATHWAY: bta04921
Entry
bta04921                    Pathway                                
Name
Oxytocin signaling pathway - Bos taurus (cow)
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
bta04921  Oxytocin signaling pathway
bta04921

Organism
Bos taurus (cow) [GN:bta]
Gene
100139857  RYR1; ryanodine receptor 1 [KO:K04961]
100295732  MAP2K5; dual specificity mitogen-activated protein kinase kinase 5 [KO:K04463] [EC:2.7.12.2]
100297344  CALM2; calmodulin-2 [KO:K02183]
100298939  HRAS; GTPase HRas isoform 1 [KO:K02833]
100337083  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X2 [KO:K05869] [EC:2.7.11.17]
100337204  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
100847184  [KO:K02833]
100848920  RGS2; regulator of G-protein signaling 2 isoform X1 [KO:K18154]
101903928  [KO:K03234]
101905399  [KO:K04368] [EC:2.7.12.2]
101906792  KCNJ4; inward rectifier potassium channel 4 [KO:K04998]
104973792  [KO:K02183]
107131237  PPP1R12B; protein phosphatase 1 regulatory subunit 12B isoform X1 [KO:K12329]
112449027  [KO:K12319] [EC:4.6.1.2]
132342877  [KO:K04873]
280795  FOS; protein c-Fos [KO:K04379]
280831  JUN; transcription factor Jun [KO:K04448]
280888  OXT; oxytocin-neurophysin 1 preproprotein [KO:K05243]
280979  ACTB; actin, cytoplasmic 1 [KO:K05692]
281138  EEF2; elongation factor 2 [KO:K03234]
281216  GUCY1A1; guanylate cyclase soluble subunit alpha-1 [KO:K12318] [EC:4.6.1.2]
281341  MYL6; myosin light polypeptide 6 [KO:K12751]
281355  NPPA; natriuretic peptides A precursor [KO:K12334]
281357  NPR2; atrial natriuretic peptide receptor 2 precursor [KO:K12324] [EC:4.6.1.2]
281371  OXTR; oxytocin receptor [KO:K04229]
281601  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
281603  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
281790  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
281791  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
281792  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
281793  GNAS; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632]
281878  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
281879  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
281883  KCNJ2; inward rectifier potassium channel 2 [KO:K04996]
281985  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
282001  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
282002  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
282023  PTGS2; prostaglandin G/H synthase 2 precursor [KO:K11987] [EC:1.14.99.1]
282041  ROCK2; rho-associated protein kinase 2 [KO:K17388] [EC:2.7.11.39]
282160  CACNB3; voltage-dependent L-type calcium channel subunit beta-3 [KO:K04864]
282161  CACNB4; voltage-dependent L-type calcium channel subunit beta-4 [KO:K04865]
282162  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
282318  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
282321  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
282322  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
282323  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
282324  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
282325  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
282433  GUCY1B1; guanylate cyclase soluble subunit beta-1 [KO:K12319] [EC:4.6.1.2]
282608  CACNA2D1; voltage-dependent calcium channel subunit alpha-2/delta-1 precursor [KO:K04858]
286800  CACNG2; voltage-dependent calcium channel gamma-2 subunit [KO:K04867]
286852  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
287024  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
287026  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
317697  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
326597  CALM; calmodulin [KO:K02183]
327667  CACNB2; voltage-dependent L-type calcium channel subunit beta-2 [KO:K04863]
327672  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
327677  CD38; ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 [KO:K01242] [EC:3.2.2.6 2.4.99.20]
327703  CACNB1; voltage-dependent L-type calcium channel subunit beta-1 [KO:K04862]
338037  MYLK; myosin light chain kinase, smooth muscle isoform 1 [KO:K00907] [EC:2.7.11.18]
338049  RHOA; transforming protein RhoA [KO:K04513]
404122  ACTG1; actin, cytoplasmic 2 [KO:K05692]
407217  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
408013  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
408015  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
504219  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
505485  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
505740  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
505964  MYL9; myosin regulatory light polypeptide 9 [KO:K12755]
506322  NRAS; GTPase NRas [KO:K07828]
508029  TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977] [EC:3.6.1.13]
508888  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
509084  CAMKK2; calcium/calmodulin-dependent protein kinase kinase 2 [KO:K07359] [EC:2.7.11.17]
509779  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
509936  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
510434  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
510708  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
511224  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
511504  CAMK1G; calcium/calmodulin-dependent protein kinase type 1G [KO:K08794] [EC:2.7.11.17]
511961  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform 1 [KO:K07200]
512254  MEF2C; myocyte-specific enhancer factor 2C [KO:K04454]
512431  PPP1R12C; protein phosphatase 1 regulatory subunit 12C isoform X1 [KO:K17457]
512665  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
513055  RGS2; regulator of G-protein signaling 2 [KO:K18154]
513497  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
515421  MYL6B; myosin light chain 6B [KO:K12751]
515621  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
515669  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
516175  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
518025  MYLK4; myosin light chain kinase family member 4 isoform X1 [KO:K00907] [EC:2.7.11.18]
519331  CACNG4; voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
519644  CACNA2D3; voltage-dependent calcium channel subunit alpha-2/delta-3 precursor [KO:K04860]
520277  CALM3; calmodulin-3 [KO:K02183]
520404  CALML5; calmodulin-like protein 5 [KO:K02183]
520498  CAMK1; calcium/calmodulin-dependent protein kinase type 1 [KO:K08794] [EC:2.7.11.17]
520743  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
521196  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
521616  CACNG6; voltage-dependent calcium channel gamma-6 subunit [KO:K04871]
521730  EEF2K; eukaryotic elongation factor 2 kinase [KO:K08292] [EC:2.7.11.20]
522866  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
524530  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
525072  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
525416  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
525482  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
526088  KCNJ3; G protein-activated inward rectifier potassium channel 1 [KO:K04997]
526364  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
526379  MYLK3; myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
526873  CAMK1D; calcium/calmodulin-dependent protein kinase type 1D isoform X1 [KO:K08794] [EC:2.7.11.17]
529382  CACNG5; voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
530001  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
530401  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
530719  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
531209  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
531391  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
532713  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
533048  NPR1; atrial natriuretic peptide receptor 1 precursor [KO:K12323] [EC:4.6.1.2]
533199  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
533378  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
533527  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
534107  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
535017  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
535603  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
535742  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
536654  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
537376  RYR2; ryanodine receptor 2 isoform X1 [KO:K04962]
537703  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
538479  KCNJ12; ATP-sensitive inward rectifier potassium channel 12 [KO:K05005]
538496  CACNG3; voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
538606  PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
538829  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
538954  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
539277  CALML4; calmodulin-like protein 4 [KO:K02183]
539521  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
539640  RCAN1; calcipressin-1 [KO:K17901]
539844  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
539899  RYR3; ryanodine receptor 3 [KO:K04963]
539969  CACNG7; voltage-dependent calcium channel gamma-7 subunit [KO:K04872]
540404  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
540740  KCNJ14; ATP-sensitive inward rectifier potassium channel 14 [KO:K05007]
541127  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333]
541140  KRAS; GTPase KRas [KO:K07827]
613600  GUCY1A2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
614838  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X3 [KO:K21290]
614969  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
617095  CALM1; calmodulin-1 [KO:K02183]
617412  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
617585  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
781184  CACNG1; voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
784075  CACNA2D4; voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
785909  CACNA2D2; voltage-dependent calcium channel subunit alpha-2/delta-2 isoform X1 [KO:K04859]
785911  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
786886  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
788119  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 [KO:K17334]
788151  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
790867  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
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
bta00590  Arachidonic acid metabolism
bta04010  MAPK signaling pathway
bta04020  Calcium signaling pathway
bta04110  Cell cycle
KO pathway
ko04921   

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