KEGG   PATHWAY: ggo04915
Entry
ggo04915                    Pathway                                
Name
Estrogen signaling pathway - Gorilla gorilla gorilla (western lowland gorilla)
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
ggo04915  Estrogen signaling pathway
ggo04915

Other DBs
GO: 0030520
Organism
Gorilla gorilla gorilla (western lowland gorilla) [GN:ggo]
Gene
101138953  ESR1; estrogen receptor isoform X1 [KO:K08550]
101142471  ESR2; estrogen receptor beta isoform X1 [KO:K08551]
101143849  HSP90AB1; heat shock protein HSP 90-beta isoform X2 [KO:K04079]
109025530  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
115936257  LOW QUALITY PROTEIN: heat shock protein HSP 90-alpha-like [KO:K04079]
109029337  heat shock protein HSP 90-beta-like [KO:K04079]
101127820  HSP90B1; endoplasmin [KO:K09487]
101143886  endoplasmin-like [KO:K09487]
101135488  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 isoform X3 [KO:K09571] [EC:5.2.1.8]
101144702  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
101134225  HSPA1A; heat shock 70 kDa protein 1A [KO:K03283]
101135640  HSPA1L; heat shock 70 kDa protein 1-like isoform X1 [KO:K03283]
101128042  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
101131586  heat shock 70 kDa protein 1A [KO:K03283]
115932977  HSPA6; heat shock 70 kDa protein 6 [KO:K03283]
101143172  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
101143868  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
101136145  NCOA3; nuclear receptor coactivator 3 isoform X2 [KO:K11256] [EC:2.3.1.48]
101136123  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
101152667  EBAG9; receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
101149486  KRT34; keratin, type I cuticular Ha4 [KO:K07604]
101154074  keratin, type I cytoskeletal 24 [KO:K07604]
101123726  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
101124458  KRT27; keratin, type I cytoskeletal 27 [KO:K07604]
101124831  KRT28; keratin, type I cytoskeletal 28 [KO:K07604]
101125196  KRT10; keratin, type I cytoskeletal 10 isoform X2 [KO:K07604]
101125918  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
101126273  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
101126626  KRT23; keratin, type I cytoskeletal 23 isoform X1 [KO:K07604]
101126989  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
101127365  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
101145065  keratin, type I cytoskeletal 17 [KO:K07604]
101145419  KRT16; keratin, type I cytoskeletal 16 [KO:K07604]
101145791  KRT31; keratin, type I cuticular Ha1 [KO:K07604]
101146156  KRT13; keratin, type I cytoskeletal 13 isoform X1 [KO:K07604]
101146725  KRT36; keratin, type I cuticular Ha6 isoform X1 [KO:K07604]
101147330  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
101147698  KRT15; keratin, type I cytoskeletal 15 isoform X1 [KO:K07604]
101148048  KRT38; keratin, type I cuticular Ha8 [KO:K07604]
101148419  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
101148777  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
101139505  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
101130743  KRT9; keratin, type I cytoskeletal 9 [KO:K07604]
101149133  keratin, type I cytoskeletal 14 [KO:K07604]
101134688  keratin, type I cytoskeletal 17-like [KO:K07604]
101124080  KRT26; keratin, type I cytoskeletal 26 [KO:K07604]
109026842  keratin, type I cuticular Ha3-II [KO:K07604]
115932656  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 16-like [KO:K07604]
115934663  KRT37; keratin, type I cuticular Ha7 [KO:K07604]
115930137  keratin, type I cuticular Ha3-I [KO:K07604]
101149839  GHAA; uncharacterized protein LOC101149839 [KO:K07604]
101126813  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 18-like [KO:K07604]
101124577  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 16-like [KO:K07604]
101140084  GREB1; protein GREB1 isoform X1 [KO:K27477]
134757838  TFF1; trefoil factor 1 [KO:K22456]
101152212  PGR; progesterone receptor isoform X1 [KO:K08556]
101140326  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
101149605  RARA; retinoic acid receptor alpha isoform X2 [KO:K08527]
101127590  FOS; protein C-Fos [KO:K04379]
101145729  JUN; transcription factor Jun [KO:K04448]
101134828  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
101132215  neuroendocrine secretory protein 55 [KO:K04632]
109023045  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X2 [KO:K04632]
101147102  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
101138361  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
101138938  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
101125943  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
101141389  ADCY2; adenylate cyclase type 2 isoform X2 [KO:K08042] [EC:4.6.1.1]
101144031  ADCY3; adenylate cyclase type 3 isoform X4 [KO:K08043] [EC:4.6.1.1]
101125890  ADCY4; adenylate cyclase type 4 isoform X6 [KO:K08044] [EC:4.6.1.1]
101139873  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
101126268  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
101142672  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101145410  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
101151469  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
101134260  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101144410  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X3 [KO:K05870]
101135003  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
101139584  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101153927  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
101128609  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
101144135  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
101144628  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
101152081  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
101153965  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X4 [KO:K09047]
101146740  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
101126190  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
101136424  SHC1; SHC-transforming protein 1 isoform X4 [KO:K06279]
101129046  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
101127418  SHC3; SHC-transforming protein 3 isoform X2 [KO:K17448]
101154420  SHC4; SHC-transforming protein 4 [KO:K17449]
101133976  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
101130824  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
101137539  SOS2; son of sevenless homolog 2 isoform X2 [KO:K03099]
101136425  HRAS; GTPase HRas isoform X1 [KO:K02833]
101144039  KRAS; GTPase KRas isoform X2 [KO:K07827]
101146562  NRAS; GTPase NRas [KO:K07828]
101136454  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X3 [KO:K04366] [EC:2.7.11.1]
101132391  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101126885  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101140164  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101135988  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101143811  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101146434  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
101152123  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101130978  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
101135298  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101129336  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
101137723  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101138019  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
101126330  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 isoform X1 [KO:K04615]
101136130  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
101125616  GNAI3; guanine nucleotide-binding protein G(I) subunit alpha-3 [KO:K04630]
101154597  GNAI1; guanine nucleotide-binding protein G(I) subunit alpha-1 isoform X1 [KO:K04630]
101150695  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
101147418  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
101141898  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
101143654  KCNJ9; G protein-activated inward rectifier potassium channel 3 isoform X1 [KO:K05002]
101150659  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
101147771  POMC; pro-opiomelanocortin [KO:K05228]
101149628  OPRM1; mu-type opioid receptor isoform X5 [KO:K04215]
101133370  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
101149651  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101140350  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X4 [KO:K05858] [EC:3.1.4.11]
101153613  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101129357  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
101154323  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X2 [KO:K05858] [EC:3.1.4.11]
101151145  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
101151502  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
101124725  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
101151475  CALML3; calmodulin-like protein 3 [KO:K02183]
101151113  CALML5; calmodulin-like protein 5 [KO:K02183]
101139397  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
101140627  calmodulin-2-like [KO:K02183]
101139013  CALM2; calmodulin-2 isoform X1 [KO:K02183]
101149474  CALM1; calmodulin-1 isoform X1 [KO:K02183]
101128007  NOS3; nitric oxide synthase 3 isoform X1 [KO:K13242] [EC:1.14.13.39]
101150458  GRM1; metabotropic glutamate receptor 1 isoform X1 [KO:K04603]
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
ggo04010  MAPK signaling pathway
ggo04020  Calcium signaling pathway
ggo04151  PI3K-Akt signaling pathway
ggo04270  Vascular smooth muscle contraction
ggo04727  GABAergic synapse
ggo04913  Ovarian steroidogenesis
KO pathway
ko04915   
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