KEGG   PATHWAY: ncar04921
Entry
ncar04921                   Pathway                                
Name
Oxytocin signaling pathway - Sciurus carolinensis (gray squirrel)
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
ncar04921  Oxytocin signaling pathway
ncar04921

Organism
Sciurus carolinensis (gray squirrel) [GN:ncar]
Gene
124977447  oxytocin-neurophysin 1-like [KO:K05243]
124977461  oxytocin-neurophysin 1 [KO:K05243]
124971102  oxytocin receptor [KO:K04229]
124964255  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
124958599  GTPase HRas isoform X1 [KO:K02833]
124991017  GTPase KRas-like [KO:K07827]
124982118  GTPase KRas isoform X1 [KO:K07827]
124962389  GTPase NRas [KO:K07828]
124971006  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
124977990  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
124969568  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
124990635  LOW QUALITY PROTEIN: mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
124970294  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
124976716  cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
124976990  cytosolic phospholipase A2 zeta-like isoform X1 [KO:K16342] [EC:3.1.1.4]
124978216  cytosolic phospholipase A2 delta-like [KO:K16342] [EC:3.1.1.4]
124978217  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
124962073  cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
124974890  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
124962420  prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
124973399  dual specificity mitogen-activated protein kinase kinase 5 isoform X1 [KO:K04463] [EC:2.7.12.2]
124980909  mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
124991717  transcription factor Jun [KO:K04448]
124963740  LOW QUALITY PROTEIN: transcription factor Jun-like [KO:K04448]
124977967  protein c-Fos [KO:K04379]
124986526  myocyte-specific enhancer factor 2C isoform X1 [KO:K04454]
124958520  G1/S-specific cyclin-D1 [KO:K04503]
124971802  ETS domain-containing protein Elk-1 [KO:K04375]
124966810  ryanodine receptor 1 isoform X1 [KO:K04961]
124961919  ryanodine receptor 2 isoform X1 [KO:K04962]
124976404  ryanodine receptor 3 [KO:K04963]
124994506  ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1-like [KO:K01242] [EC:3.2.2.6 2.4.99.20]
124992449  LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily M member 2-like [KO:K04977] [EC:3.6.1.13]
124980775  inward rectifier potassium channel 2 [KO:K04996]
124980914  ATP-sensitive inward rectifier potassium channel 12 isoform X1 [KO:K05005]
124983410  inward rectifier potassium channel 4 [KO:K04998]
124966830  ATP-sensitive inward rectifier potassium channel 14 [KO:K05007]
124976705  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
124959812  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
124977474  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
124972679  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
124979014  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
124970211  LOW QUALITY PROTEIN: protein kinase C beta type-like [KO:K19662] [EC:2.7.11.13]
124967611  protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
124970151  eukaryotic elongation factor 2 kinase [KO:K08292] [EC:2.7.11.20]
124968834  elongation factor 2 [KO:K03234]
124982084  voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
124968359  LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D-like [KO:K04851]
124971751  voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
124961645  voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
124980591  voltage-dependent L-type calcium channel subunit beta-1 isoform X1 [KO:K04862]
124961976  LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit beta-2-like [KO:K04863]
124982456  LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit beta-3-like [KO:K04864]
124979835  voltage-dependent L-type calcium channel subunit beta-4 isoform X1 [KO:K04865]
124990321  voltage-dependent calcium channel subunit alpha-2/delta-1 isoform X1 [KO:K04858]
124992864  voltage-dependent calcium channel subunit alpha-2/delta-2 isoform X1 [KO:K04859]
124969140  voltage-dependent calcium channel subunit alpha-2/delta-3 isoform X1 [KO:K04860]
124982731  voltage-dependent calcium channel subunit alpha-2/delta-4 [KO:K04861]
124980463  voltage-dependent calcium channel gamma-1 subunit [KO:K04866]
124982217  voltage-dependent calcium channel gamma-2 subunit isoform X1 [KO:K04867]
124970546  voltage-dependent calcium channel gamma-3 subunit [KO:K04868]
124981165  voltage-dependent calcium channel gamma-4 subunit [KO:K04869]
124980471  voltage-dependent calcium channel gamma-5 subunit [KO:K04870]
124966274  voltage-dependent calcium channel gamma-6 subunit [KO:K04871]
124966037  voltage-dependent calcium channel gamma-7 subunit isoform X1 [KO:K04872]
124967101  voltage-dependent calcium channel gamma-8 subunit [KO:K04873]
124970932  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
124983533  inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
124988553  inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
124976834  LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
124967357  calmodulin-1 [KO:K02183]
124967948  calmodulin-like protein 6 [KO:K02183]
124962006  calmodulin-like [KO:K02183]
124962112  calmodulin-A-like [KO:K02183]
124962222  calmodulin-like protein 3 [KO:K02183]
124963056  calmodulin-1 [KO:K02183]
124976085  calmodulin-1 [KO:K02183]
124994051  serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
124984768  serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
124982403  serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
124963548  calcineurin subunit B type 1 [KO:K06268]
124963939  calcineurin subunit B type 2 [KO:K06268]
124965416  LOW QUALITY PROTEIN: nuclear factor of activated T-cells, cytoplasmic 1-like [KO:K04446]
124977074  LOW QUALITY PROTEIN: nuclear factor of activated T-cells, cytoplasmic 2-like [KO:K17332]
124966545  LOW QUALITY PROTEIN: nuclear factor of activated T-cells, cytoplasmic 3-like [KO:K17333]
124976754  nuclear factor of activated T-cells, cytoplasmic 4 isoform X1 [KO:K17334]
124962362  regulator of G-protein signaling 2 [KO:K18154]
124992930  calcipressin-1 isoform X1 [KO:K17901]
124975873  calcipressin-1-like [KO:K17901]
124990307  calcium/calmodulin-dependent protein kinase kinase 2 isoform X1 [KO:K07359] [EC:2.7.11.17]
124987007  5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
124983683  5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
124990233  5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
124960770  5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
124990239  5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
124980693  5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
124983681  5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
124961680  calcium/calmodulin-dependent protein kinase type 1D isoform X1 [KO:K08794] [EC:2.7.11.17]
124961928  calcium/calmodulin-dependent protein kinase type 1G [KO:K08794] [EC:2.7.11.17]
124971021  calcium/calmodulin-dependent protein kinase type 1 [KO:K08794] [EC:2.7.11.17]
124985817  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
124986742  calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
124994412  calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
124990768  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
124987181  calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
124990691  nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
124994911  guanylate cyclase soluble subunit alpha-1 [KO:K12318] [EC:4.6.1.2]
124959976  guanylate cyclase soluble subunit alpha-2 isoform X1 [KO:K12318] [EC:4.6.1.2]
124985555  guanylate cyclase soluble subunit beta-2-like [KO:K12319] [EC:4.6.1.2]
124995059  guanylate cyclase soluble subunit beta-1 isoform X1 [KO:K12319] [EC:4.6.1.2]
124963564  natriuretic peptides A-like [KO:K12334]
124961045  atrial natriuretic peptide receptor 1 isoform X1 [KO:K12323] [EC:4.6.1.2]
124964609  atrial natriuretic peptide receptor 2 isoform X1 [KO:K12324] [EC:4.6.1.2]
124992643  myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
124989613  myosin light chain kinase family member 4-like isoform X1 [KO:K00907] [EC:2.7.11.18]
124966787  myosin light chain kinase 3-like isoform X1 [KO:K00907] [EC:2.7.11.18]
124978195  myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
124981957  myosin light chain 6B [KO:K12751]
124981958  myosin light polypeptide 6 isoform X1 [KO:K12751]
124983885  myosin light chain 6B-like [KO:K12751]
124977953  myosin regulatory light polypeptide 9 [KO:K12755]
124958454  actin, muscle-like [KO:K05692]
124976675  actin, cytoplasmic 2-like [KO:K05692]
124984855  actin, cytoplasmic 1-like [KO:K05692]
124969779  actin, cytoplasmic 1 [KO:K05692]
124979796  actin, cytoplasmic 2 [KO:K05692]
124971792  actin, cytoplasmic 1-like [KO:K05692]
124982432  actin, cytoplasmic 1-like [KO:K05692]
124993416  transforming protein RhoA [KO:K04513]
124989136  transforming protein RhoA-like isoform X1 [KO:K04513]
124976920  transforming protein RhoA-like [KO:K04513]
124965296  rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
124962770  rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
124991738  serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
124960013  serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
124963007  serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
124982345  protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270]
124961505  protein phosphatase 1 regulatory subunit 12B isoform X1 [KO:K12329]
124966901  protein phosphatase 1 regulatory subunit 12C isoform X1 [KO:K17457]
124978161  neuroendocrine secretory protein 55 [KO:K04632]
124975134  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
124990345  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
124987010  adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
124962927  adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
124978229  LOW QUALITY PROTEIN: adenylate cyclase type 4-like [KO:K08044] [EC:4.6.1.1]
124992559  adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
124983776  adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
124966834  adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
124965096  adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
124970113  LOW QUALITY PROTEIN: adenylate cyclase type 9-like [KO:K08049] [EC:4.6.1.1]
124985819  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
124969119  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
124992673  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
124988012  guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
124991078  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
124967520  guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
124991973  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
124980224  phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
124981277  phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
124977049  proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
124980509  G protein-activated inward rectifier potassium channel 1 [KO:K04997]
124993028  G protein-activated inward rectifier potassium channel 2 [KO:K05000]
124990924  G protein-activated inward rectifier potassium channel 3 [KO:K05002]
124960772  G protein-activated inward rectifier potassium channel 4 isoform X1 [KO:K04999]
124990601  epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
124989493  cyclin-dependent kinase inhibitor 1-like [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
ncar00590  Arachidonic acid metabolism
ncar04010  MAPK signaling pathway
ncar04020  Calcium signaling pathway
ncar04110  Cell cycle
KO pathway
ko04921   
LinkDB

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