KEGG   PATHWAY: ptg04921
Entry
ptg04921                    Pathway                                
Name
Oxytocin signaling pathway - Panthera tigris altaica (Amur tiger)
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
ptg04921  Oxytocin signaling pathway
ptg04921

Organism
Panthera tigris altaica (Amur tiger) [GN:ptg]
Gene
102956999  OXTR; oxytocin receptor [KO:K04229]
102954227  GNAQ; G protein subunit alpha q [KO:K04634]
102952119  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102957350  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102952980  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102955852  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102969757  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102956808  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102964841  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102960964  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102964036  PLA2G4D; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]
102959937  PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
102959018  PLA2G4B; phospholipase A2 group IVB [KO:K16342] [EC:3.1.1.4]
102959667  PLA2G4E; phospholipase A2 group IVE [KO:K16342] [EC:3.1.1.4]
102948969  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
102948685  PTGS2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]
102949008  MAP2K5; mitogen-activated protein kinase kinase 5 [KO:K04463] [EC:2.7.12.2]
102964803  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
102958666  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
102952769  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
102962519  MEF2C; myocyte enhancer factor 2C [KO:K04454]
102959906  CCND1; cyclin D1 [KO:K04503]
102966062  ELK1; ELK1, ETS transcription factor [KO:K04375]
102971670  RYR1; ryanodine receptor 1 [KO:K04961]
102963018  RYR2; ryanodine receptor 2 [KO:K04962]
102961931  RYR3; ryanodine receptor 3 [KO:K04963]
102955186  CD38; CD38 molecule [KO:K01242] [EC:3.2.2.6 2.4.99.20]
102970544  TRPM2; transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
102967064  KCNJ2; potassium voltage-gated channel subfamily J member 2 [KO:K04996]
102950237  ATP-sensitive inward rectifier potassium channel 12 [KO:K05005]
102972555  KCNJ4; potassium voltage-gated channel subfamily J member 4 [KO:K04998]
102959485  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
102961437  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
102960646  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
102961121  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
102968590  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
102952814  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
102956490  PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
102960729  EEF2K; eukaryotic elongation factor 2 kinase [KO:K08292] [EC:2.7.11.20]
102959442  EEF2; eukaryotic translation elongation factor 2 [KO:K03234]
102956322  CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
102958456  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
102950547  CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
102949808  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
102958190  voltage-dependent L-type calcium channel subunit beta-1 [KO:K04862]
102965296  CACNB2; calcium voltage-gated channel auxiliary subunit beta 2 [KO:K04863]
102949738  CACNB3; calcium voltage-gated channel auxiliary subunit beta 3 [KO:K04864]
102953668  CACNB4; calcium voltage-gated channel auxiliary subunit beta 4 [KO:K04865]
102951633  CACNA2D1; calcium voltage-gated channel auxiliary subunit alpha2delta 1 [KO:K04858]
102967999  CACNA2D2; calcium voltage-gated channel auxiliary subunit alpha2delta 2 [KO:K04859]
102957490  CACNA2D3; calcium voltage-gated channel auxiliary subunit alpha2delta 3 [KO:K04860]
102951140  CACNA2D4; calcium voltage-gated channel auxiliary subunit alpha2delta 4 [KO:K04861]
102967997  CACNG1; calcium voltage-gated channel auxiliary subunit gamma 1 [KO:K04866]
102963348  CACNG2; calcium voltage-gated channel auxiliary subunit gamma 2 [KO:K04867]
102957309  CACNG3; calcium voltage-gated channel auxiliary subunit gamma 3 [KO:K04868]
102961689  CACNG5; calcium voltage-gated channel auxiliary subunit gamma 5 [KO:K04870]
102956783  CACNG6; calcium voltage-gated channel auxiliary subunit gamma 6 [KO:K04871]
102948563  CACNG7; calcium voltage-gated channel auxiliary subunit gamma 7 [KO:K04872]
102963245  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102971840  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102967639  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102953457  CALM3; calmodulin 3 [KO:K02183]
102963939  calmodulin-like [KO:K02183]
102964234  CALML3; calmodulin-like protein 3 [KO:K02183]
102954552  CALM2; calmodulin 2 [KO:K02183]
102960923  calmodulin-like [KO:K02183]
102950842  CALML6; calmodulin like 6 [KO:K02183]
102951822  CALM1; calmodulin 1 [KO:K02183]
102971520  calmodulin-alpha-like [KO:K02183]
102950182  CALML4; calmodulin like 4 [KO:K02183]
102952632  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
102949359  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
102963447  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
102965200  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
102967427  PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
102969678  NFATC2; nuclear factor of activated T-cells 2 [KO:K17332]
102972106  NFATC3; nuclear factor of activated T-cells 3 [KO:K17333]
102956831  NFATC4; nuclear factor of activated T-cells 4 [KO:K17334]
102966001  RGS2; regulator of G-protein signaling 2 [KO:K18154]
102961978  RCAN1; regulator of calcineurin 1 [KO:K17901]
102971870  CAMKK2; calcium/calmodulin dependent protein kinase kinase 2 [KO:K07359] [EC:2.7.11.17]
102970831  PRKAA2; protein kinase AMP-activated catalytic subunit alpha 2 [KO:K07198] [EC:2.7.11.31]
102956343  PRKAA1; protein kinase AMP-activated catalytic subunit alpha 1 [KO:K07198] [EC:2.7.11.31]
102972403  PRKAB2; protein kinase AMP-activated non-catalytic subunit beta 2 [KO:K07199]
102952112  PRKAB1; protein kinase AMP-activated non-catalytic subunit beta 1 [KO:K07199]
102951896  PRKAG1; protein kinase AMP-activated non-catalytic subunit gamma 1 [KO:K07200]
102960269  PRKAG2; protein kinase AMP-activated non-catalytic subunit gamma 2 [KO:K07200]
102959115  PRKAG3; protein kinase AMP-activated non-catalytic subunit gamma 3 [KO:K07200]
102961856  CAMK1D; calcium/calmodulin dependent protein kinase ID [KO:K08794] [EC:2.7.11.17]
102966233  CAMK1G; calcium/calmodulin dependent protein kinase IG [KO:K08794] [EC:2.7.11.17]
102969115  CAMK1; calcium/calmodulin dependent protein kinase I [KO:K08794] [EC:2.7.11.17]
102964851  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
102966494  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
102957556  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
102950197  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
102954895  CAMK4; calcium/calmodulin dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
102967516  NOS3; nitric oxide synthase 3 [KO:K13242] [EC:1.14.13.39]
102969669  GUCY1A3; guanylate cyclase 1 soluble subunit alpha [KO:K12318] [EC:4.6.1.2]
102956040  GUCY1A2; guanylate cyclase 1 soluble subunit alpha 2 [KO:K12318] [EC:4.6.1.2]
102963951  GUCY1B3; guanylate cyclase 1 soluble subunit beta [KO:K12319] [EC:4.6.1.2]
102970885  guanylate cyclase soluble subunit beta-2-like [KO:K12319] [EC:4.6.1.2]
102969166  NPPA; natriuretic peptide A [KO:K12334]
102949070  NPR2; natriuretic peptide receptor 2 [KO:K12324] [EC:4.6.1.2]
102951994  MYLK2; myosin light chain kinase 2 [KO:K00907] [EC:2.7.11.18]
102962607  MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
102968305  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
102972928  MYLK; myosin light chain kinase [KO:K00907] [EC:2.7.11.18]
102963650  MYL6B; myosin light chain 6B [KO:K12751]
102964235  MYL6; myosin light chain 6 [KO:K12751]
102964789  MYL9; myosin light chain 9 [KO:K12755]
102971629  ACTG1; actin gamma 1 [KO:K05692]
102971401  ACTB; actin beta [KO:K05692]
102952555  RHOA; ras homolog family member A [KO:K04513]
102963520  ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.1]
102949986  ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.1]
102948702  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
107180886  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
102970154  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
102951696  PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
102950482  PPP1R12B; protein phosphatase 1 regulatory subunit 12B [KO:K12329]
102964615  PPP1R12C; protein phosphatase 1 regulatory subunit 12C [KO:K17457]
102964541  GNAS; GNAS complex locus [KO:K04632]
102961712  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
102949732  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
102965866  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
102969833  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
102949044  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
102972917  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
102948581  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
102969003  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
102948983  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102972158  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
102954501  GNAI1; G protein subunit alpha i1 [KO:K04630]
102951159  GNAI3; G protein subunit alpha i3 [KO:K04630]
102962946  GNAI2; G protein subunit alpha i2 [KO:K04630]
102958483  GNAO1; G protein subunit alpha o1 [KO:K04534]
102953306  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
102954383  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
102954665  PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290]
102968822  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
102959759  G protein-activated inward rectifier potassium channel 1 [KO:K04997]
102966763  G protein-activated inward rectifier potassium channel 2 [KO:K05000]
102965302  KCNJ5; potassium voltage-gated channel subfamily J member 5 [KO:K04999]
102967370  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102964051  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
ptg00590  Arachidonic acid metabolism
ptg04010  MAPK signaling pathway
ptg04020  Calcium signaling pathway
ptg04110  Cell cycle
KO pathway
ko04921   
LinkDB

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