Myometrial relaxation and contraction pathways (Homo sapiens)

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1-3Activation via CRH and cAMPPPKC inhibitor 1Pathways of Myometrial ContractionNOTRMg2+TRPhospholipase-CCalcium MobilizationCell GrowthRGSPKCNucleusEts complexPi + Camk2Camk2TR Calcium InfluxNa+GbgRegulators of G-proteinsignaling (RGS)PKC inhibitor 1GbgLPAAdenylyl CyclasesGbgNa+PKCMyometrial ContractionPhospholipase-CIGFBPCa2+Pathways of Myometrial RelaxationTranscription FactorsSRPip2Predicted OT-RCa2+Pge2IGFBPMyometrial RelaxationIP3Predicted Cxn43Adenylyl CyclasesDAGAP-1 complexTranscriptional RegulationMAPKCREB1GUCA2BCALM2YWHABIGFBP6ACTG1GUCY1A3PRKCB1GNB1PKIAATF4PKIBCAMK2BGRK4LGR7GNASCALM1YWHAGATF3IGFBP3GSTO1ETS2MYL4GABPB2ITPR3CREB3RGS7IL6PRKCGOXTRARRB1RGS4CRHACTA1GJA1CAMK2AATPRYR3ADCY6ATF5YWHAHPKIGYWHAENOS1CRHR1RYR1MAFFADMGRK5YWHAQNFKB1GNG12GNG8GNB5CAMK2DPDE4DPRKD1CORINATP2A3ADCY4LGR8SFNNOS3PLCB3RGS6Cyclic GMPGRK6IGFBP4ADMRADCY1ATPRAMP1ADCY7GNB2RYR2ATF1ADPGNB3RGS16GNG13GRK4ADPCAMK2GPRKCQATP2A2GRK5RGS20PRKACBGNG5GUCA2ARLN1GABPAPRKCDCNN1PDE4BPRKACAPRKAR2BPRKCZRGS5MYLK2EDG2RGS2ARRB2CACNB3JUNRGS14PLCD1MYLK2OXTRRAMP2GNG11GNGT1ITPR2ARRB1ADCY8ACTCOXTGUCY2EGNAQRAMP3MYL2SLC8A1ADCY2ARRB2RGS9Cyclic AMPRGS17CMKOR1FOSIL1BGNB4PLCG1Cyclic AMPPRKCEPRKAR2ACALCAADCY3IGFBP5RGS19ADCY5YWHAZATF2GNG2RCP9PRKCHGNG3PRKCACALM3ACTA2IGFBP2ITPR1RGS3GNG4PLCG2CREBL1CNN2RGS10ACTBPRKAR1BDGKZRGS18ADCY9SP1PRKAR1ARGS11IGFBP1GNG7RGS1CALD1GRK6


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.

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Ontology Terms

 

Bibliography

  1. 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
  2. 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
  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
126283view04:34, 20 April 2023EgonwLicense is CCZero
122789view00:34, 18 May 2022AlexanderPicocleaning up broken comments
120734view12:47, 27 December 2021EweitzRefine label positions, case
116545view12:14, 7 May 2021EweitzModified title
107347view19:37, 26 September 2019Khanspersfixed unconnected
106652view21:14, 12 September 2019KhanspersModified description
106149view12:04, 16 August 2019MaintBotHMDB identifier normalization
105653view05:13, 10 August 2019KhanspersModified description
102527view01:21, 4 January 2019Khanspersconverted interaction to graphical line
96894view13:53, 18 April 2018FehrhartConnected lines
89548view11:34, 16 September 2016Mkutmonremove invalid ontology tag
89543view11:30, 16 September 2016MkutmonOntology Term : 'DOID:9219' removed !
81078view04:54, 21 July 2015EgonwFixed weird characters in autors names.
80212view21:02, 22 May 2015KhanspersReverted to version '10:30, 7 January 2015' by Khanspers
80169view22:33, 14 May 2015KhanspersAdded mir219 targeting of CAMK2G
78540view10:30, 7 January 2015MaintBotadded missing graphIds
72107view22:09, 24 October 2013AlexanderPicoRemoved PRKCC; it is an alias of PRKCG
71563view19:29, 17 October 2013MaintBotremoved data source from nodes without identifier
69917view19:40, 11 July 2013MaintBotupdated to 2013 schema
45373view21:19, 7 October 2011KhanspersOntology Term : 'smooth muscle cell' added !
44933view10:58, 6 October 2011MartijnVanIerselOntology Term : 'signaling pathway' added !
44932view10:57, 6 October 2011MartijnVanIerselOntology Term : 'pregnancy complication' added !
41146view23:40, 1 March 2011MaintBotRemoved redundant pathway information and comments
38942view22:28, 24 September 2010NsalomonisSpecify description
38941view22:27, 24 September 2010NsalomonisSpecify description
38940view22:24, 24 September 2010NsalomonisModified description
38939view22:22, 24 September 2010NsalomonisModified description
38911view20:47, 24 September 2010AlexanderPico
38909view20:45, 24 September 2010AlexanderPicoSpecify description
38896view19:59, 24 September 2010AlexanderPicominor tweaks
38895view19:57, 24 September 2010AlexanderPicomajor curation: updating complexes, groups and aliases
38871view18:28, 24 September 2010KhanspersChanged line tyeps
38870view18:26, 24 September 2010Khanspers
35257view20:13, 11 February 2010Thomasmoved references from comment to bibliography
34434view18:14, 10 December 2009MaintBotAutomatic update of empty xrefs
32386view16:57, 15 August 2009MaintBotFixed text labels
32029view13:25, 14 August 2009MaintBotFixed group labels
21289view11:31, 14 November 2008MaintBot[[Pathway:Homo sapiens:Smooth muscle contraction]] moved to [[Pathway:WP289]]: Moved to stable identifier
20135view12:23, 21 October 2008Thomaslinked some unconnected lines
16754view23:28, 26 June 2008KhanspersAdded metabolits
13994view15:04, 20 May 2008Thomas
13909view19:06, 19 May 2008AlexanderPicofix attempt 3
13907view19:00, 19 May 2008AlexanderPicomoved label
13905view18:59, 19 May 2008AlexanderPicofix attempt 2
13903view18:57, 19 May 2008AlexanderPicofix attempt 1
13868view07:21, 19 May 2008AlexanderPicominor tweak
13865view07:12, 19 May 2008AlexanderPicoconnectors test2
13863view07:04, 19 May 2008AlexanderPicoReverted to version '04:17, 17 May 2008' by AlexanderPico
13861view07:02, 19 May 2008AlexanderPicoconnector test
13117view11:17, 17 May 2008MaintBotautomated metabolite conversion

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ACTA1GeneProduct58 (Entrez Gene)
ACTA2GeneProduct59 (Entrez Gene)
ACTBGeneProduct60 (Entrez Gene)
ACTCGeneProduct70 (Entrez Gene)
ACTG1GeneProduct71 (Entrez Gene)
ADCY1GeneProduct107 (Entrez Gene) CYA1 HUMAN
ADCY2GeneProduct108 (Entrez Gene) There is no SwissProt entry for a full-length sequence in mouse. This EST is from the Affymetrix Murine6500 chip.
ADCY3GeneProduct109 (Entrez Gene)
ADCY4GeneProduct196883 (Entrez Gene) There is no SwissProt entry for a full-length sequence in mouse. This EST is from the Affymetrix Murine6500 chip.
ADCY5GeneProduct111 (Entrez Gene) There is no SwissProt entry for a full-length sequence in mouse. This EST is from the Affymetrix Murine6500 chip.
ADCY6GeneProduct112 (Entrez Gene)
ADCY7GeneProduct113 (Entrez Gene)
ADCY8GeneProduct114 (Entrez Gene)
ADCY9GeneProduct115 (Entrez Gene)
ADMGeneProduct133 (Entrez Gene)
ADMRGeneProduct11318 (Entrez Gene)
ADPMetabolite58-64-0 (CAS)
ARRB1GeneProduct408 (Entrez Gene)
ARRB2GeneProduct409 (Entrez Gene)
ATF1GeneProduct466 (Entrez Gene)
ATF2GeneProduct1386 (Entrez Gene)
ATF3GeneProduct467 (Entrez Gene)
ATF4GeneProduct468 (Entrez Gene)
ATF5GeneProduct22809 (Entrez Gene)
ATPMetabolite1927-31-7 (CAS)
ATP2A2GeneProduct488 (Entrez Gene)
ATP2A3GeneProduct489 (Entrez Gene)
CACNB3GeneProduct784 (Entrez Gene)
CALCAGeneProduct796 (Entrez Gene) CRF HUMAN PMID: 11854458
CALD1GeneProduct800 (Entrez Gene)
CALM1GeneProduct801 (Entrez Gene)
CALM2GeneProduct805 (Entrez Gene)
CALM3GeneProduct808 (Entrez Gene)
CAMK2AGeneProduct815 (Entrez Gene)
CAMK2BGeneProduct816 (Entrez Gene)
CAMK2DGeneProduct817 (Entrez Gene)
CAMK2GGeneProduct818 (Entrez Gene)
CMKOR1GeneProduct57007 (Entrez Gene) PMID: 10614663
CNN1GeneProduct1264 (Entrez Gene)
CNN2GeneProduct1265 (Entrez Gene)
CORINGeneProduct10699 (Entrez Gene) MGI:97367
CREB1GeneProduct1385 (Entrez Gene)
CREB3GeneProduct10488 (Entrez Gene)
CREBL1GeneProduct1388 (Entrez Gene)
CRHGeneProduct1392 (Entrez Gene) CRF HUMAN PMID: 11854458
CRHR1GeneProduct1394 (Entrez Gene)
Cyclic AMPMetaboliteHMDB00058 (HMDB)
Cyclic GMPMetaboliteHMDB01314 (HMDB)
DGKZGeneProduct8525 (Entrez Gene)
EDG2GeneProduct1902 (Entrez Gene)
ETS2GeneProduct2114 (Entrez Gene)
FOSGeneProduct2353 (Entrez Gene) PMID: 10218980 PMID: 7628395 [
GABPAGeneProduct2551 (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
GABPB2GeneProduct2553 (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
GJA1GeneProduct2697 (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
GNAQGeneProduct2776 (Entrez Gene)
GNASGeneProduct2778 (Entrez Gene)
GNB1GeneProduct2782 (Entrez Gene)
GNB2GeneProduct2783 (Entrez Gene)
GNB3GeneProduct2784 (Entrez Gene)
GNB4GeneProduct59345 (Entrez Gene)
GNB5GeneProduct10681 (Entrez Gene)
GNG11GeneProduct2791 (Entrez Gene)
GNG12GeneProduct55970 (Entrez Gene)
GNG13GeneProduct51764 (Entrez Gene)
GNG2GeneProduct54331 (Entrez Gene)
GNG3GeneProduct2785 (Entrez Gene)
GNG4GeneProduct2786 (Entrez Gene)
GNG5GeneProduct2787 (Entrez Gene)
GNG7GeneProduct2788 (Entrez Gene)
GNG8GeneProduct94235 (Entrez Gene)
GNGT1GeneProduct2792 (Entrez Gene)
GRK4GeneProduct2868 (Entrez Gene)
GRK5GeneProduct2869 (Entrez Gene)
GRK6GeneProduct2870 (Entrez Gene)
GSTO1GeneProduct9446 (Entrez Gene)
GUCA2AGeneProduct2980 (Entrez Gene)
GUCA2BGeneProduct2981 (Entrez Gene)
GUCY1A3GeneProduct2982 (Entrez Gene) PMID: 11854458
GUCY2EGeneProduct2985 (Entrez Gene) PMID: 11854458
IGFBP1GeneProduct3484 (Entrez Gene)
IGFBP2GeneProduct3485 (Entrez Gene)
IGFBP3GeneProduct3486 (Entrez Gene) Relaxin is a member of the Insulin Growth Factor family of proteins. IGFBP-3 binds IGFII preferentially. (SwissProt).
IGFBP4GeneProduct3487 (Entrez Gene)
IGFBP5GeneProduct3488 (Entrez Gene)
IGFBP6GeneProduct3489 (Entrez Gene)
IL1BGeneProduct3553 (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.
IL6GeneProduct3569 (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.
ITPR1GeneProduct3708 (Entrez Gene)
ITPR2GeneProduct3709 (Entrez Gene)
ITPR3GeneProduct3710 (Entrez Gene)
JUNGeneProduct3725 (Entrez Gene) PMID: 10218980
LGR7GeneProduct59350 (Entrez Gene) PMID: 11809971
LGR8GeneProduct122042 (Entrez Gene) PMID: 11809971 LGR8 MOUSE
MAFFGeneProduct23764 (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.
MYL2GeneProduct4633 (Entrez Gene)
MYL4GeneProduct4635 (Entrez Gene)
MYLK2GeneProduct85366 (Entrez Gene) KML2 MOUSE
NFKB1GeneProduct4790 (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
NOS1GeneProduct4842 (Entrez Gene) PMID: 11854458
NOS3GeneProduct4846 (Entrez Gene) PMID: 11854458
OXTGeneProduct5020 (Entrez Gene) MGI:97453
OXTRGeneProduct5021 (Entrez Gene)
PDE4BGeneProduct5142 (Entrez Gene)
PDE4DGeneProduct5144 (Entrez Gene)
PKIAGeneProduct5569 (Entrez Gene)
PKIBGeneProduct5570 (Entrez Gene)
PKIGGeneProduct11142 (Entrez Gene)
PLCB3GeneProduct5331 (Entrez Gene)
PLCD1GeneProduct5333 (Entrez Gene)
PLCG1GeneProduct5335 (Entrez Gene)
PLCG2GeneProduct5336 (Entrez Gene)
PRKACAGeneProduct5566 (Entrez Gene)
PRKACBGeneProduct5567 (Entrez Gene)
PRKAR1AGeneProduct5573 (Entrez Gene) KAP0 HUMAN
PRKAR1BGeneProduct5575 (Entrez Gene)
PRKAR2AGeneProduct5576 (Entrez Gene)
PRKAR2BGeneProduct5577 (Entrez Gene)
PRKCAGeneProduct5578 (Entrez Gene)
PRKCB1GeneProduct5579 (Entrez Gene)
PRKCDGeneProduct5580 (Entrez Gene)
PRKCEGeneProduct5581 (Entrez Gene) This EST is listed on the Affymetrix Murine6500 chip. The SwissProt entry name is KPCE MOUSE.
PRKCGGeneProduct5582 (Entrez Gene)
PRKCHGeneProduct5583 (Entrez Gene)
PRKCQGeneProduct5588 (Entrez Gene)
PRKCZGeneProduct5590 (Entrez Gene)
PRKD1GeneProduct5587 (Entrez Gene) KPCM HUMAN
RAMP1GeneProduct10267 (Entrez Gene)
RAMP2GeneProduct10266 (Entrez Gene)
RAMP3GeneProduct10268 (Entrez Gene)
RCP9GeneProduct27297 (Entrez Gene)
RGS10GeneProduct6001 (Entrez Gene)
RGS11GeneProduct8786 (Entrez Gene)
RGS14GeneProduct10636 (Entrez Gene)
RGS1GeneProduct5996 (Entrez Gene)
RGS16GeneProduct6004 (Entrez Gene)
RGS17GeneProduct26575 (Entrez Gene)
RGS18GeneProduct64407 (Entrez Gene)
RGS19GeneProduct10287 (Entrez Gene)
RGS20GeneProduct8601 (Entrez Gene)
RGS2GeneProduct5997 (Entrez Gene)
RGS3GeneProduct5998 (Entrez Gene)
RGS4GeneProduct5999 (Entrez Gene)
RGS5GeneProduct8490 (Entrez Gene)
RGS6GeneProduct9628 (Entrez Gene)
RGS7GeneProduct6000 (Entrez Gene)
RGS9GeneProduct8787 (Entrez Gene)
RLN1GeneProduct6013 (Entrez Gene)
RYR1GeneProduct6261 (Entrez Gene)
RYR2GeneProduct6262 (Entrez Gene)
RYR3GeneProduct6263 (Entrez Gene)
SFNGeneProduct2810 (Entrez Gene)
SLC8A1GeneProduct6546 (Entrez Gene)
SP1GeneProduct6667 (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
YWHABGeneProduct7529 (Entrez Gene)
YWHAEGeneProduct7531 (Entrez Gene)
YWHAGGeneProduct7532 (Entrez Gene)
YWHAHGeneProduct7533 (Entrez Gene)
YWHAQGeneProduct10971 (Entrez Gene)
YWHAZGeneProduct7534 (Entrez Gene) PMID: 9861170 PMID: 1317796

Annotated Interactions

No annotated interactions

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