KEGG   PATHWAY: cpoc04915
Entry
cpoc04915                   Pathway                                
Name
Estrogen signaling pathway - Cavia porcellus (domestic guinea pig)
Description
Estrogens are steroid hormones that regulate a plethora of physiological processes in mammals, including reproduction, cardiovascular protection, bone integrity, cellular homeostasis, and behavior. Estrogen mediates its cellular actions through two signaling pathways classified as "nuclear-initiated steroid signaling" and "membrane-initiated steroid signaling". In the "nuclear" pathway, estrogen binds either ERalpha or ERbeta, which in turn translocates to the nucleus, binds DNA at ERE elements and activates the expression of ERE-dependent genes. In "membrane" pathway, Estrogen can exert its actions through a subpopulation of ER at the plasma membrane (mER) or novel G-protein coupled E2 receptors (GPER). Upon activation of these receptors various signaling pathways (i.e. Ca2+, cAMP, protein kinase cascades) are rapidly activated and ultimately influence downstream transcription factors.
Class
Organismal Systems; Endocrine system
Pathway map
cpoc04915  Estrogen signaling pathway
cpoc04915

Other DBs
GO: 0030520
Organism
Cavia porcellus (domestic guinea pig) [GN:cpoc]
Gene
100135528  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
100135529  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
100135530  Gnai3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
100135577  Nos3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
100135584  Nras; GTPase NRas [KO:K07828]
100169689  Krt12; keratin, type I cytoskeletal 12 [KO:K07604]
100169692  Calm3; calmodulin [KO:K02183]
100170763  Gabbr1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
100170764  Gabbr2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
100190980  Kcnj3; LOW QUALITY PROTEIN: G protein-activated inward rectifier potassium channel 1 [KO:K04997]
100379267  Oprm1; mu-type opioid receptor [KO:K04215]
100712633  [KO:K07604]
100712694  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
100712730  Krt35; keratin, type I cuticular Ha5 [KO:K07604]
100712743  Gper1; G-protein coupled estrogen receptor 1 [KO:K04246]
100712888  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
100712907  Krt36; keratin, type I cuticular Ha6 isoform X1 [KO:K07604]
100712996  [KO:K07604]
100713023  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
100713183  Krt13; keratin, type I cytoskeletal 13 isoform X1 [KO:K07604]
100713247  Greb1; protein GREB1 isoform X1 [KO:K27477]
100713272  [KO:K07604]
100713276  Esr1; estrogen receptor [KO:K08550]
100713456  [KO:K07604]
100713547  [KO:K07604]
100713572  Fos; proto-oncogene c-Fos [KO:K04379]
100713734  Krt9; keratin, type I cytoskeletal 9 [KO:K07604]
100713849  Hspa8; heat shock cognate 71 kDa protein [KO:K03283]
100713963  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
100714013  [KO:K07604]
100714143  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X4 [KO:K05858] [EC:3.1.4.11]
100714547  Kcnj6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
100714586  [KO:K04634]
100714724  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100714732  Adcy5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
100715119  Hspa6; heat shock 70 kDa protein 6 [KO:K03283]
100715180  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100715453  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
100715532  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
100715672  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100716262  Kras; GTPase KRas isoform X3 [KO:K07827]
100716648  Gnao1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
100717205  [KO:K03283]
100717226  Adcy9; adenylate cyclase type 9 isoform X2 [KO:K08049] [EC:4.6.1.1]
100717278  Itpr2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100717481  [KO:K03283]
100717842  Shc4; SHC-transforming protein 4 [KO:K17449]
100718451  Fkbp4; LOW QUALITY PROTEIN: peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
100719318  Creb5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
100719361  Mmp2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
100719925  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100720110  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
100720622  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100720803  Pomc; pro-opiomelanocortin [KO:K05228]
100721165  Sos1; LOW QUALITY PROTEIN: son of sevenless homolog 1 [KO:K03099]
100722340  Adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
100722552  Kcnj5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
100722913  Ncoa1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
100723025  [KO:K17447]
100723767  Hsp90b1; endoplasmin isoform X2 [KO:K09487]
100724035  Fkbp5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
100724163  Ebag9; receptor-binding cancer antigen expressed on SiSo cells isoform X1 [KO:K22455]
100724214  Calm2; calmodulin [KO:K02183]
100724315  Akt3; LOW QUALITY PROTEIN: RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100724945  Pgr; LOW QUALITY PROTEIN: progesterone receptor [KO:K08556]
100725363  Egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
100725667  Adcy3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
100725692  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100725824  [KO:K04079]
100726398  Sos2; son of sevenless homolog 2 [KO:K03099]
100726500  Sp1; transcription factor Sp1 isoform X2 [KO:K04684]
100726624  Prkcd; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
100726699  Adcy7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
100726889  Atf2; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
100726957  Atf6b; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
100727326  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X2 [KO:K05870]
100727662  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
100727986  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
100728220  Rara; retinoic acid receptor alpha isoform X2 [KO:K08527]
100728342  Calml3; calmodulin-like protein 3 [KO:K02183]
100728509  Src; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
100728510  Mmp9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
100728625  [KO:K02183]
100728649  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X5 [KO:K09048]
100728775  Jun; LOW QUALITY PROTEIN: transcription factor AP-1 [KO:K04448]
100728923  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100728965  Krt25; keratin, type I cytoskeletal 25 [KO:K07604]
100729184  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X2 [KO:K04960]
100729246  Kcnj9; LOW QUALITY PROTEIN: G protein-activated inward rectifier potassium channel 3 [KO:K05002]
100729248  [KO:K07604]
100729390  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
100729394  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
100729464  [KO:K03283]
100729525  [KO:K07604]
100729712  [KO:K02183]
100729798  Krt39; keratin, type I cytoskeletal 39 [KO:K07604]
100729935  Hsp90ab1; heat shock protein HSP 90-beta [KO:K04079]
100730066  Krt23; keratin, type I cytoskeletal 23 [KO:K07604]
100730149  Calml4; calmodulin-like protein 4 isoform X1 [KO:K02183]
100730242  Pik3r1; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
100730572  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
100730891  Grm1; metabotropic glutamate receptor 1 [KO:K04603]
100731200  Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
100731224  Adcy6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
100731304  Esr2; estrogen receptor beta [KO:K08551]
100731681  Hbegf; proheparin-binding EGF-like growth factor isoform X2 [KO:K08523]
100731822  [KO:K07604]
100731999  Adcy2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
100732091  [KO:K07604]
100732095  Ncoa3; LOW QUALITY PROTEIN: nuclear receptor coactivator 3 [KO:K11256] [EC:2.3.1.48]
100732158  [KO:K04632]
100732296  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100732336  Shc3; SHC-transforming protein 3 [KO:K17448]
100732369  [KO:K07604]
100732436  [KO:K04632]
100732651  Krt40; keratin, type I cytoskeletal 40 [KO:K07604]
100733337  Bcl2; LOW QUALITY PROTEIN: apoptosis regulator Bcl-2 [KO:K02161]
100733372  Hsp90aa1; heat shock protein HSP 90-alpha [KO:K04079]
100734044  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100734206  [KO:K02649]
100734327  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
100734544  Calm1; calmodulin-1 [KO:K02183]
100734561  Shc1; SHC-transforming protein 1 isoform X2 [KO:K06279]
100735038  Hras; GTPase HRas isoform X1 [KO:K02833]
100735084  Pik3ca; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100735429  Ncoa2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
100735694  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
100735735  Ctsd; cathepsin D [KO:K01379] [EC:3.4.23.5]
100735821  [KO:K07604]
100735962  Krt18; keratin, type I cytoskeletal 18 [KO:K07604]
100736005  [KO:K07604]
100736104  [KO:K07604]
101788006  Krt24; keratin, type I cytoskeletal 24 [KO:K07604]
106027819  Calml6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
111755957  [KO:K07604]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C00238  Potassium cation
C00334  4-Aminobutanoate
C00533  Nitric oxide
C00575  3',5'-Cyclic AMP
C00951  Estradiol-17beta
C01245  D-myo-Inositol 1,4,5-trisphosphate
Reference
PMID:16516516
  Authors
Zhang D, Trudeau VL
  Title
Integration of membrane and nuclear estrogen receptor signaling.
  Journal
Comp Biochem Physiol A Mol Integr Physiol 144:306-15 (2006)
DOI:10.1016/j.cbpa.2006.01.025
Reference
PMID:19187465
  Authors
Roepke TA, Qiu J, Bosch MA, Ronnekleiv OK, Kelly MJ
  Title
Cross-talk between membrane-initiated and nuclear-initiated oestrogen signalling in the hypothalamus.
  Journal
J Neuroendocrinol 21:263-70 (2009)
DOI:10.1111/j.1365-2826.2009.01846.x
Reference
PMID:19700741
  Authors
McCarthy MM
  Title
The two faces of estradiol: effects on the developing brain.
  Journal
Neuroscientist 15:599-610 (2009)
DOI:10.1177/1073858409340924
Reference
PMID:18538919
  Authors
Kelly MJ, Ronnekleiv OK
  Title
Membrane-initiated estrogen signaling in hypothalamic neurons.
  Journal
Mol Cell Endocrinol 290:14-23 (2008)
DOI:10.1016/j.mce.2008.04.014
Reference
PMID:16112267
  Authors
Kelly MJ, Qiu J, Ronnekleiv OK
  Title
Estrogen signaling in the hypothalamus.
  Journal
Vitam Horm 71:123-45 (2005)
DOI:10.1016/S0083-6729(05)71005-0
Reference
PMID:18253054
  Authors
Raz L, Khan MM, Mahesh VB, Vadlamudi RK, Brann DW
  Title
Rapid estrogen signaling in the brain.
  Journal
Neurosignals 16:140-53 (2008)
DOI:10.1159/000111559
Reference
PMID:15862823
  Authors
Malyala A, Kelly MJ, Ronnekleiv OK
  Title
Estrogen modulation of hypothalamic neurons: activation of multiple signaling pathways and gene expression changes.
  Journal
Steroids 70:397-406 (2005)
DOI:10.1016/j.steroids.2005.03.004
Reference
PMID:14573532
  Authors
Qiu J, Bosch MA, Tobias SC, Grandy DK, Scanlan TS, Ronnekleiv OK, Kelly MJ
  Title
Rapid signaling of estrogen in hypothalamic neurons involves a novel G-protein-coupled estrogen receptor that activates protein kinase C.
  Journal
J Neurosci 23:9529-40 (2003)
DOI:10.1523/JNEUROSCI.23-29-09529.2003
Reference
PMID:14993035
  Authors
Kelly MJ, Qiu J, Ronnekleiv OK
  Title
Estrogen modulation of G-protein-coupled receptor activation of potassium channels in the central nervous system.
  Journal
Ann N Y Acad Sci 1007:6-16 (2003)
DOI:10.1196/annals.1286.001
Reference
PMID:19549587
  Authors
Meyer MR, Haas E, Prossnitz ER, Barton M
  Title
Non-genomic regulation of vascular cell function and growth by estrogen.
  Journal
Mol Cell Endocrinol 308:9-16 (2009)
DOI:10.1016/j.mce.2009.03.009
Reference
PMID:20694192
  Authors
do Nascimento GR, Barros YV, Wells AK, Khalil RA
  Title
Research into Specific Modulators of Vascular Sex Hormone Receptors in the Management of Postmenopausal Cardiovascular Disease.
  Journal
Curr Hypertens Rev 5:283-306 (2009)
DOI:10.2174/157340209789587717
Reference
PMID:15695368
  Authors
Bjornstrom L, Sjoberg M
  Title
Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes.
  Journal
Mol Endocrinol 19:833-42 (2005)
DOI:10.1210/me.2004-0486
Reference
PMID:16270355
  Authors
Manavathi B, Kumar R
  Title
Steering estrogen signals from the plasma membrane to the nucleus: two sides of the coin.
  Journal
J Cell Physiol 207:594-604 (2006)
DOI:10.1002/jcp.20551
Reference
PMID:21844907
  Authors
Prossnitz ER, Barton M
  Title
The G-protein-coupled estrogen receptor GPER in health and disease.
  Journal
Nat Rev Endocrinol 7:715-26 (2011)
DOI:10.1038/nrendo.2011.122
Reference
PMID:21742056
  Authors
Meyer MR, Prossnitz ER, Barton M
  Title
The G protein-coupled estrogen receptor GPER/GPR30 as a regulator of cardiovascular function.
  Journal
Vascul Pharmacol 55:17-25 (2011)
DOI:10.1016/j.vph.2011.06.003
Reference
PMID:19767412
  Authors
Maggiolini M, Picard D
  Title
The unfolding stories of GPR30, a new membrane-bound estrogen receptor.
  Journal
J Endocrinol 204:105-14 (2010)
DOI:10.1677/JOE-09-0242
Reference
PMID:19464786
  Authors
Prossnitz ER, Maggiolini M
  Title
Mechanisms of estrogen signaling and gene expression via GPR30.
  Journal
Mol Cell Endocrinol 308:32-8 (2009)
DOI:10.1016/j.mce.2009.03.026
Reference
PMID:12650715
  Authors
Kelly MJ, Qiu J, Wagner EJ, Ronnekleiv OK
  Title
Rapid effects of estrogen on G protein-coupled receptor activation of potassium channels in the central nervous system (CNS).
  Journal
J Steroid Biochem Mol Biol 83:187-93 (2002)
DOI:10.1016/S0960-0760(02)00249-2
Reference
PMID:9278514
  Authors
Paech K, Webb P, Kuiper GG, Nilsson S, Gustafsson J, Kushner PJ, Scanlan TS
  Title
Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites.
  Journal
Science 277:1508-10 (1997)
DOI:10.1126/science.277.5331.1508
Reference
PMID:12421825
  Authors
Razandi M, Pedram A, Park ST, Levin ER
  Title
Proximal events in signaling by plasma membrane estrogen receptors.
  Journal
J Biol Chem 278:2701-12 (2003)
DOI:10.1074/jbc.M205692200
Reference
PMID:18755790
  Authors
Roepke TA, Xue C, Bosch MA, Scanlan TS, Kelly MJ, Ronnekleiv OK
  Title
Genes associated with membrane-initiated signaling of estrogen and energy homeostasis.
  Journal
Endocrinology 149:6113-24 (2008)
DOI:10.1210/en.2008-0769
Reference
PMID:21779010
  Authors
Thomas C, Gustafsson JA
  Title
The different roles of ER subtypes in cancer biology and therapy.
  Journal
Nat Rev Cancer 11:597-608 (2011)
DOI:10.1038/nrc3093
Related
pathway
cpoc04010  MAPK signaling pathway
cpoc04020  Calcium signaling pathway
cpoc04151  PI3K-Akt signaling pathway
cpoc04270  Vascular smooth muscle contraction
cpoc04727  GABAergic synapse
cpoc04913  Ovarian steroidogenesis
KO pathway
ko04915   

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