Myometrial relaxation and contraction pathways (Mus musculus)

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Nucleus1, 2CytosolPredicted OT-RCell GrowthGbgPKC inhibitor Protein-1DAGRegulators of G-proteinCAM-Kinase 2Ets complexGbgPathways of Myometrial RelaxationCa2+Adenylyl CyclasesPge2NOPredicted Cxn43Mg2+CalmodulinSignalingRAMPnote: see gene backpages for referencesMlckPathways of Myometrial ContractionGPCR Kinasebeta ArrestinGRKbeta ArrestinPKARAMPPhospholipase-CCRE-Transcription FactorsIGFBPMAPKCalcium MobilizationGRKbeta ArrestinIP3TR = Transcriptional RegulationPip2PKCIP3 ReceptorRGSMyometrial ContractionRyrSRCa++/CalmodulinLPAProtein Kinase CRyanodine Receptor (Ryr)Ca2+TranscriptionalRegulatorsProtein Kinase ACalcium InfluxMyometrial RelaxationTRPIGFBPAdenylyl CyclasesCamk2PKA InhibitorsTRGbgIP3 ReceptorAP-1 complexPKC inhibitor 1Phospholipase-CNa+Activation Via CRH and cAMPCyclic GMPAdcy2Crhr1Itpr2Ets2Gnb4Atf3CorinATPIgfbp2Adcy9YwhabLpar1Adcy7Rgs4Acta1Acta2CrcpYwhazActbPrkacbGng11Arrb1Prkd1Rgs7Rgs1PrkchCalcaGuca2aGnasRgs19Nfkb1Rgs6PrkczPrkciPlcd1Mylk2Adcy6Rgs16YwhahRgs2DgkzRgs11Arrb2PrkcbGucy2eActg1PrkacaGsto1Adcy1Rgs14GnaqGnb2Gng2Myl4CrhAdcy3Gng3PkigRxfp1Itpr3Grk4Atf4Rgs3Ramp3Adcy4Igfbp4OxtAdcy5Cacnb3Sp1Camk2aGnb3Prkar2aGabpaFosMaffGucy1a3Rgs20Prkar1aCalm1JunPlcg1SfnCamk2gGngt1PrkceRyr2Cyclic AMPGng7Ryr1PrkcdGrk6Atf1Grk5Ramp2Gng12Rgs9OxtrRgs5Plcg2Actc1Gng4PrkcqPkiaCyclic AMPCnn1Rxfp2Ramp1Nos3ADPCalm2PrkcgCald1Igfbp3Prkar1bCnn2Il1bGng5Itpr1PkibMyl2AdmRgs18Gnb1Gng13Camk2dCalm3Gng8OxtrYwhaeIgfbp5Pde4dPrkcaGm2423Ryr3Il6Plcb3Rgs10Rln1Gpr182Cxcr7Nos1Pde4bGabpb1Creb1Atp2a3YwhagAtf5Adcy8ATPGnb5Gja1Camk2bAtf2Slc8a1Guca2bADPAtp2a2Rgs17Igfbp1Prkar2bCreb3Atf6bIgfbp6


Description

This pathway illustrates signaling networks implicated in uterine muscle contraction at labor and quiescence throughout gestation (pregnancy). The muscle of the uterus, responsible for contractile activity is the myometrium. Genes in this pathway are either transcribed in myometrial muscle cells or act upon the myometrium to regulate contraction. The left half of this pathway illustrates pathways of myometrial relaxation that are active throughout normal gestation. These signaling events act to suppress coordinated contractions to prevent the early onset of labor at term, largely via activation of the adenylyl-cyclase thrhough G-protein coupled receptors. On the right side of this pathway are signaling componets involved in the activation of uterine contractions at labor, in particular, activation of calcium mobilization via Oxytocin mediated binding to the Oxytocin G-protein coupled receptor. Additional genes implicated in this pathway, based on microarray expression profiling of gestation, term and postpartum of term mice are also included (e.g., Guca2b, Rdc1, Edg2) have also been included. For a detailed description of this pathway see: http://genomebiology.com/2005/6/2/R12.

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP289(r21289) with a 90% conversion rate.

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Ontology Terms

 

Bibliography

  1. Méhats C, Tanguy G, Dallot E, Cabrol D, Ferré F, Leroy MJ; ''Is up-regulation of phosphodiesterase 4 activity by PGE2 involved in the desensitization of beta-mimetics in late pregnancy human myometrium?''; J Clin Endocrinol Metab, 2001 PubMed Europe PMC Scholia
  2. Salomonis N, Cotte N, Zambon AC, Pollard KS, Vranizan K, Doniger SW, Dolganov G, Conklin BR; ''Identifying genetic networks underlying myometrial transition to labor.''; Genome Biol, 2005 PubMed Europe PMC Scholia
  3. Aggelidou E, Hillhouse EW, Grammatopoulos DK; ''Up-regulation of nitric oxide synthase and modulation of the guanylate cyclase activity by corticotropin-releasing hormone but not urocortin II or urocortin III in cultured human pregnant myometrial cells.''; Proc Natl Acad Sci U S A, 2002 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
122794view01:27, 18 May 2022AlexanderPicocleaning up broken comments
122793view01:25, 18 May 2022AlexanderPicocleaning up broken comments
117920view10:35, 23 May 2021EweitzModified title
114015view15:02, 17 December 2020Fehrhartconnected unconnected lines
109383view15:28, 16 March 2020L DupuisFixed interactions
106886view13:36, 17 September 2019MaintBotHMDB identifier normalization
95806view14:53, 19 January 2018MkutmonHomology conversion update
87897view12:53, 25 July 2016ElisaOntology Term : 'signaling pathway' added !
72108view22:11, 24 October 2013AlexanderPicoupdating label: Prkcc to Prkcg
72046view16:46, 24 October 2013Mkutmonupdated annotations
69916view19:38, 11 July 2013MaintBotModified description
69913view19:37, 11 July 2013MaintBotupdating to 2013 schema
47969view13:36, 23 April 2012MartijnVanIerseladded cell
47968view13:34, 23 April 2012MartijnVanIersellayout, added nucleus
47772view05:36, 6 April 2012Khanspersupdated xref
41284view00:22, 2 March 2011MaintBotRemoved redundant pathway information and comments
35258view20:16, 11 February 2010Thomasmoved references from comment to bibliography
34385view22:49, 9 December 2009MaintBotAutomatic update of empty xrefs
32693view23:21, 31 August 2009KhanspersAdded ATP xref
32692view23:20, 31 August 2009Khanspersadded xrefs
32417view17:07, 15 August 2009MaintBotFixed text labels
32074view13:37, 14 August 2009MaintBotFixed group labels
31445view21:08, 13 August 2009MaintBotFixed text labels
30819view23:57, 29 July 2009MaintBotConverted from Homo sapiens
21488view11:31, 14 November 2008MaintBot[[Pathway:Mus musculus:Smooth muscle contraction]] moved to [[Pathway:WP385]]: Moved to stable identifier
8398view13:46, 7 January 2008MaintBot[[Pathway:Mouse:Smooth muscle contraction]] moved to [[Pathway:Mus musculus:Smooth muscle contraction]]: Renaming species
7816view16:19, 18 December 2007MaintBotfixed category names
7489view12:42, 4 November 2007MaintBotAdded categories to GPML
6495view22:19, 22 May 2007Nsalomonisgpml file for [[Mouse:Smooth_muscle_contraction]]

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADPMetaboliteHMDB01341 (HMDB)
ATPMetabolite1927-31-7 (CAS)
Acta1GeneProduct11459 (Entrez Gene)
Acta2GeneProduct11475 (Entrez Gene)
ActbGeneProduct11461 (Entrez Gene)
Actc1GeneProduct11464 (Entrez Gene)
Actg1GeneProduct11465 (Entrez Gene)
Adcy1GeneProduct432530 (Entrez Gene) CYA1 HUMAN
Adcy2GeneProduct210044 (Entrez Gene) There is no SwissProt entry for a full-length sequence in mouse. This EST is from the Affymetrix Murine6500 chip.
Adcy3GeneProduct104111 (Entrez Gene)
Adcy4GeneProduct104110 (Entrez Gene) There is no SwissProt entry for a full-length sequence in mouse. This EST is from the Affymetrix Murine6500 chip.
Adcy5GeneProduct224129 (Entrez Gene) There is no SwissProt entry for a full-length sequence in mouse. This EST is from the Affymetrix Murine6500 chip.
Adcy6GeneProduct11512 (Entrez Gene)
Adcy7GeneProduct11513 (Entrez Gene)
Adcy8GeneProduct11514 (Entrez Gene)
Adcy9GeneProduct11515 (Entrez Gene)
AdmGeneProduct11535 (Entrez Gene)
Arrb1GeneProduct109689 (Entrez Gene)
Arrb2GeneProduct216869 (Entrez Gene)
Atf1GeneProduct11908 (Entrez Gene)
Atf2GeneProduct11909 (Entrez Gene)
Atf3GeneProduct11910 (Entrez Gene)
Atf4GeneProduct11911 (Entrez Gene)
Atf5GeneProduct107503 (Entrez Gene)
Atf6bGeneProduct12915 (Entrez Gene)
Atp2a2GeneProduct11938 (Entrez Gene)
Atp2a3GeneProduct53313 (Entrez Gene)
Cacnb3GeneProduct12297 (Entrez Gene)
CalcaGeneProduct12310 (Entrez Gene) CRF HUMAN PMID: 11854458
Cald1GeneProduct109624 (Entrez Gene)
Calm1GeneProduct12313 (Entrez Gene)
Calm2GeneProduct12314 (Entrez Gene)
Calm3GeneProduct12315 (Entrez Gene)
Camk2aGeneProduct12322 (Entrez Gene)
Camk2bGeneProduct12323 (Entrez Gene)
Camk2dGeneProduct108058 (Entrez Gene)
Camk2gGeneProduct12325 (Entrez Gene)
Cnn1GeneProduct12797 (Entrez Gene)
Cnn2GeneProduct12798 (Entrez Gene)
CorinGeneProduct53419 (Entrez Gene) MGI:97367
CrcpGeneProduct12909 (Entrez Gene)
Creb1GeneProduct12912 (Entrez Gene)
Creb3GeneProduct12913 (Entrez Gene)
CrhGeneProduct12918 (Entrez Gene) CRF HUMAN PMID: 11854458
Crhr1GeneProduct12921 (Entrez Gene)
Cxcr7GeneProduct12778 (Entrez Gene) PMID: 10614663
Cyclic AMPMetaboliteHMDB00058 (HMDB)
Cyclic GMPMetaboliteHMDB01314 (HMDB)
DgkzGeneProduct104418 (Entrez Gene)
Ets2GeneProduct23872 (Entrez Gene)
FosGeneProduct14281 (Entrez Gene) PMID: 10218980 PMID: 7628395 [
GabpaGeneProduct14390 (Entrez Gene) Identification of a GABP alpha/beta binding site involved in the induction of oxytocin receptor gene expression in human breast cells, potentiation by c-Fos/c-Jun.

Hoare S, Copland JA, Wood TG, Jeng YJ, Izban MG, Soloff MS.

PMID: 10218980
Gabpb1GeneProduct14391 (Entrez Gene) Identification of a GABP alpha/beta binding site involved in the induction of oxytocin receptor gene expression in human breast cells, potentiation by c-Fos/c-Jun.

Hoare S, Copland JA, Wood TG, Jeng YJ, Izban MG, Soloff MS.

PMID: 10218980
Gja1GeneProduct14609 (Entrez Gene) Endogenous nitric oxide suppresses rat myometrial connexin 43 gap junction protein expression during pregnancy.

Sladek SM, Westerhausen-Larson A, Roberts JM.

PMID: 10377025
Gm2423GeneProductENSMUSG00000061724 (Ensembl)
GnaqGeneProduct14682 (Entrez Gene)
GnasGeneProduct14683 (Entrez Gene)
Gnb1GeneProduct14688 (Entrez Gene)
Gnb2GeneProduct14693 (Entrez Gene)
Gnb3GeneProduct14695 (Entrez Gene)
Gnb4GeneProduct14696 (Entrez Gene)
Gnb5GeneProduct14697 (Entrez Gene)
Gng11GeneProduct66066 (Entrez Gene)
Gng12GeneProduct14701 (Entrez Gene)
Gng13GeneProduct64337 (Entrez Gene)
Gng2GeneProduct14702 (Entrez Gene)
Gng3GeneProduct14704 (Entrez Gene)
Gng4GeneProduct14706 (Entrez Gene)
Gng5GeneProduct14707 (Entrez Gene)
Gng7GeneProduct14708 (Entrez Gene)
Gng8GeneProduct14709 (Entrez Gene)
Gngt1GeneProduct14699 (Entrez Gene)
Gpr182GeneProduct11536 (Entrez Gene)
Grk4GeneProduct14772 (Entrez Gene)
Grk5GeneProduct14773 (Entrez Gene)
Grk6GeneProduct26385 (Entrez Gene)
Gsto1GeneProduct14873 (Entrez Gene)
Guca2aGeneProduct14915 (Entrez Gene)
Guca2bGeneProduct14916 (Entrez Gene)
Gucy1a3GeneProduct60596 (Entrez Gene) PMID: 11854458
Gucy2eGeneProduct14919 (Entrez Gene) PMID: 11854458
Igfbp1GeneProduct16006 (Entrez Gene)
Igfbp2GeneProduct16008 (Entrez Gene)
Igfbp3GeneProduct16009 (Entrez Gene) Relaxin is a member of the Insulin Growth Factor family of proteins. IGFBP-3 binds IGFII preferentially. (SwissProt).
Igfbp4GeneProduct16010 (Entrez Gene)
Igfbp5GeneProduct16011 (Entrez Gene)
Igfbp6GeneProduct16012 (Entrez Gene)
Il1bGeneProduct16176 (Entrez Gene) Structure, characterization, and expression of the rat oxytocin receptor gene.

Rozen F, Russo C, Banville D, Zingg HH PMID: 7816817 quote: The presence of APREs in the OTR gene promoter suggests that the acute induction of OTR expression at the onset of parturition may be a phenomenon mechanistically similar to the fast induction of acute phase response genes. This notion is strengthened by the observation that the uterus is populated by macrophages and other specific lymphocytes (19,20). Specifically, at term, nearly half of the decidual cells are of bone marrow origin (20). IL-1beta released from macrophages stimulates the production and release of IL-6 by uterine stromal cells (21,22). Moreover, IL- is a central pathophysiological mediator of infection-induced premature delivery (23), and preterm delivery can be prevented by an IL-1 antagonist in mice (24). We speculate that under physiological as well as phathophysiological conditions, inflammatory cytokines are important inducers of labor and that this mechanism involves the cytokine-induced transcriptional activation of the OTR gene. :end quote

19. Hunt, J.S. (1994) Biol. Reprod. 50, 461-466 20. Vince, G.S., et al. (1990) J. Immunol. Methods 132, 181-189. 21. Tabibzadeh, S. (1991) Endocr. Rev, 12, 272-290. 22. Dudley, D.Jl, et. Al. (1992) J. Clin. Endocrinol. Metab. 74, 884-889 23. Romero, R., et. Al, Am. J. Obstet. Gynecol. 167, 863-872.

Il6GeneProduct16193 (Entrez Gene) Structure, characterization, and expression of the rat oxytocin receptor gene.

Rozen F, Russo C, Banville D, Zingg HH PMID: 7816817 quote: The presence of APREs in the OTR gene promoter suggests that the acute induction of OTR expression at the onset of parturition may be a phenomenon mechanistically similar to the fast induction of acute phase response genes. This notion is strengthened by the observation that the uterus is populated by macrophages and other specific lymphocytes (19,20). Specifically, at term, nearly half of the decidual cells are of bone marrow origin (20). IL-1beta released from macrophages stimulates the production and release of IL-6 by uterine stromal cells (21,22). Moreover, IL- is a central pathophysiological mediator of infection-induced premature delivery (23), and preterm delivery can be prevented by an IL-1 antagonist in mice (24). We speculate that under physiological as well as phathophysiological conditions, inflammatory cytokines are important inducers of labor and that this mechanism involves the cytokine-induced transcriptional activation of the OTR gene. :end quote

19. Hunt, J.S. (1994) Biol. Reprod. 50, 461-466 20. Vince, G.S., et al. (1990) J. Immunol. Methods 132, 181-189. 21. Tabibzadeh, S. (1991) Endocr. Rev, 12, 272-290. 22. Dudley, D.Jl, et. Al. (1992) J. Clin. Endocrinol. Metab. 74, 884-889 23. Romero, R., et. Al, Am. J. Obstet. Gynecol. 167, 863-872.

Itpr1GeneProduct16438 (Entrez Gene)
Itpr2GeneProduct16439 (Entrez Gene)
Itpr3GeneProduct16440 (Entrez Gene)
JunGeneProduct16476 (Entrez Gene) PMID: 10218980
Lpar1GeneProduct14745 (Entrez Gene)
MaffGeneProduct17133 (Entrez Gene) OMIM: Inoue et al. (1994) demonstrated that the US-2 element in the promoter of the human oxytocin receptor gene (OXTR; 167055) binds specifically nuclear proteins from human myometrium at parturition. Using the US-2 element in a yeast 1-hybrid system to screen a human myometrium cDNA library, Kimura et al. (1999) isolated a full-length cDNA encoding the homolog of chicken MafF. Human MAFF encodes a deduced 164-amino acid protein with a predicted molecular mass of 17.8 kD. Like other small MAF proteins (e.g., MAFG, 602020), it contains an extended leucine zipper structure and lacks an N-terminal transactivating domain. Northern blot analysis showed a strong 2.6-kb signal in mRNA from term myometrium and from kidney, but not from nonpregnant myometrium. The MAFF protein is also preferentially expressed in term myometrium. The authors concluded that MAFF plays a role in OXTR gene upregulation at term.
Myl2GeneProduct17906 (Entrez Gene)
Myl4GeneProduct17896 (Entrez Gene)
Mylk2GeneProduct228785 (Entrez Gene) KML2 MOUSE
Nfkb1GeneProduct18033 (Entrez Gene) Localization of regulatory protein binding sites in the proximal region of human myometrial connexin 43 gene. Echetebu CO, Ali M, Izban MG, MacKay L, Garfield RE. PMID: 10421804
Nos1GeneProduct18125 (Entrez Gene) PMID: 11854458
Nos3GeneProduct18127 (Entrez Gene) PMID: 11854458
OxtGeneProduct18429 (Entrez Gene) MGI:97453
OxtrGeneProduct18430 (Entrez Gene)

Sladek SM, Westerhausen-Larson A, Roberts JM.

PMID: 10377025
Pde4bGeneProduct18578 (Entrez Gene)
Pde4dGeneProduct238871 (Entrez Gene)
PkiaGeneProduct18767 (Entrez Gene)
PkibGeneProduct18768 (Entrez Gene)
PkigGeneProduct18769 (Entrez Gene)
Plcb3GeneProduct18797 (Entrez Gene)
Plcd1GeneProduct18799 (Entrez Gene)
Plcg1GeneProduct18803 (Entrez Gene)
Plcg2GeneProduct234779 (Entrez Gene)
PrkacaGeneProduct18747 (Entrez Gene)
PrkacbGeneProduct18749 (Entrez Gene)
Prkar1aGeneProduct19084 (Entrez Gene) KAP0 HUMAN
Prkar1bGeneProduct19085 (Entrez Gene)
Prkar2aGeneProduct19087 (Entrez Gene)
Prkar2bGeneProduct19088 (Entrez Gene)
PrkcaGeneProduct18750 (Entrez Gene)
PrkcbGeneProduct18751 (Entrez Gene)
PrkcdGeneProduct18753 (Entrez Gene)
PrkceGeneProduct18754 (Entrez Gene) This EST is listed on the Affymetrix Murine6500 chip. The SwissProt entry name is KPCE MOUSE.
PrkcgGeneProduct18752 (Entrez Gene)
PrkchGeneProduct18755 (Entrez Gene)
PrkciGeneProduct18759 (Entrez Gene)
PrkcqGeneProduct18761 (Entrez Gene)
PrkczGeneProduct18762 (Entrez Gene)
Prkd1GeneProduct18760 (Entrez Gene) KPCM HUMAN
Ramp1GeneProduct51801 (Entrez Gene)
Ramp2GeneProduct54409 (Entrez Gene)
Ramp3GeneProduct56089 (Entrez Gene)
Rgs10GeneProduct67865 (Entrez Gene)
Rgs11GeneProduct50782 (Entrez Gene)
Rgs14GeneProduct51791 (Entrez Gene)
Rgs1GeneProduct50778 (Entrez Gene)
Rgs16GeneProduct19734 (Entrez Gene)
Rgs17GeneProduct56533 (Entrez Gene)
Rgs18GeneProduct64214 (Entrez Gene)
Rgs19GeneProduct56470 (Entrez Gene)
Rgs20GeneProduct58175 (Entrez Gene)
Rgs2GeneProduct19735 (Entrez Gene)
Rgs3GeneProduct50780 (Entrez Gene)
Rgs4GeneProduct19736 (Entrez Gene)
Rgs5GeneProduct19737 (Entrez Gene)
Rgs6GeneProduct50779 (Entrez Gene)
Rgs7GeneProduct24012 (Entrez Gene)
Rgs9GeneProduct19739 (Entrez Gene)
Rln1GeneProduct19773 (Entrez Gene)
Rxfp1GeneProduct381489 (Entrez Gene) PMID: 11809971
Rxfp2GeneProduct140498 (Entrez Gene) PMID: 11809971 LGR8 MOUSE
Ryr1GeneProduct20190 (Entrez Gene)
Ryr2GeneProduct20191 (Entrez Gene)
Ryr3GeneProduct20192 (Entrez Gene)
SfnGeneProduct55948 (Entrez Gene)
Slc8a1GeneProduct20541 (Entrez Gene)
Sp1GeneProduct20683 (Entrez Gene) Promoter activity of the rat connexin 43 gene in NRK cells.

Fernandez-Cobo M, Stewart D, Drujan D, De Maio A.

Division of Pediatric Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

PMID: 11255234
YwhabGeneProduct54401 (Entrez Gene)
YwhaeGeneProduct22627 (Entrez Gene)
YwhagGeneProduct22628 (Entrez Gene)
YwhahGeneProduct22629 (Entrez Gene)
YwhazGeneProduct22631 (Entrez Gene) PMID: 9861170 PMID: 1317796

Annotated Interactions

No annotated interactions
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