KEGG   PATHWAY: npo04915
Entry
npo04915                    Pathway                                
Name
Estrogen signaling pathway - Nyctereutes procyonoides (raccoon dog)
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
npo04915  Estrogen signaling pathway
npo04915

Other DBs
GO: 0030520
Organism
Nyctereutes procyonoides (raccoon dog) [GN:npo]
Gene
129500554  ESR1; estrogen receptor [KO:K08550]
129496007  ESR2; estrogen receptor beta [KO:K08551]
129494639  LOW QUALITY PROTEIN: heat shock protein HSP 90-beta-like [KO:K04079]
129496348  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
129513069  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
129516837  HSP90B1; endoplasmin [KO:K09487]
129503397  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
129513139  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
129503012  heat shock cognate 71 kDa protein [KO:K03283]
129496819  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
129512479  heat shock 70 kDa protein 1-like isoform X1 [KO:K03283]
129512480  heat shock 70 kDa protein 1 [KO:K03283]
129512788  heat shock 70 kDa protein 1 [KO:K03283]
129514743  heat shock cognate 71 kDa protein-like [KO:K03283]
129510902  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
129505208  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
129495688  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
129495480  apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
129514527  apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
129502655  EBAG9; receptor-binding cancer antigen expressed on SiSo cells isoform X1 [KO:K22455]
129517156  LOW QUALITY PROTEIN: receptor-binding cancer antigen expressed on SiSo cells-like [KO:K22455]
129508159  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
129509031  keratin, type I cytoskeletal 42 [KO:K07604]
129503553  KRT24; keratin, type I cytoskeletal 24 [KO:K07604]
129506924  KRT38; keratin, type I cuticular Ha8 [KO:K07604]
129506930  keratin, type I cytoskeletal 13 isoform X1 [KO:K07604]
129506938  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
129506974  keratin, type I cuticular Ha7-like [KO:K07604]
129506985  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
129506991  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
129506996  keratin, type I cuticular Ha8-like [KO:K07604]
129507002  keratin, type I cuticular Ha1 [KO:K07604]
129515201  keratin, type I cytoskeletal 14 [KO:K07604]
129515702  KRT33A; keratin, type I cuticular Ha3-I [KO:K07604]
129515822  KRT28; keratin, type I cytoskeletal 28 [KO:K07604]
129515827  keratin, type I cytoskeletal 27 [KO:K07604]
129515830  keratin, type I cytoskeletal 26-like [KO:K07604]
129515837  keratin, type I cytoskeletal 25 [KO:K07604]
129515841  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
129516226  keratin, type I cuticular Ha1-like [KO:K07604]
129516466  keratin, type I cytoskeletal 17 [KO:K07604]
129516838  KRT9; keratin, type I cytoskeletal 9 [KO:K07604]
129517035  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
129517347  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
129517774  keratin, type I cytoskeletal 16 [KO:K07604]
129518073  keratin, type I cytoskeletal 18-like [KO:K07604]
129512874  KRT15; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 15 [KO:K07604]
129519902  keratin, type I cytoskeletal 18 [KO:K07604]
129512881  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
129514482  keratin, type I cuticular Ha3-II [KO:K07604]
129514741  KRT20; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 20 [KO:K07604]
129514753  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
129514763  KRT10; keratin, type I cytoskeletal 10 isoform X1 [KO:K07604]
129503059  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
129510726  GREB1; protein GREB1 [KO:K27477]
129506795  PGR; progesterone receptor isoform X1 [KO:K08556]
129511504  TGFA; protransforming growth factor alpha [KO:K08774]
129504221  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
129496401  FOS; protein c-Fos [KO:K04379]
129497811  JUN; transcription factor Jun [KO:K04448]
129517345  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
129519546  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
129497792  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
129497848  neuroendocrine secretory protein 55 [KO:K04632]
129512833  guanine nucleotide-binding protein G(s) subunit alpha-like isoform X1 [KO:K04632]
129494438  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
129513683  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
129496726  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
129514009  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
129515724  LOW QUALITY PROTEIN: adenylate cyclase type 1-like [KO:K08041] [EC:4.6.1.1]
129516202  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
129498939  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
129510932  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
129499511  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
129503910  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
129517234  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
129513386  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
129502672  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
129519450  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
129519960  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
129521768  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
129522997  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
129518269  cyclic AMP-responsive element-binding protein 1-like [KO:K05870]
129498595  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
129511576  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
129508719  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
129494799  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
129503105  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
129515926  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
129522278  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
129502771  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
129513003  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
129494118  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
129508769  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
129522289  SHC2; SHC-transforming protein 2 [KO:K17447]
129500459  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
129506392  SHC4; SHC-transforming protein 4 [KO:K17449]
129511906  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
129496132  SOS2; son of sevenless homolog 2 [KO:K03099]
129510881  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
129494224  HRAS; GTPase HRas isoform X1 [KO:K02833]
129505561  KRAS; GTPase KRas isoform X1 [KO:K07827]
129501466  NRAS; GTPase NRas [KO:K07828]
129522592  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
129506345  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
129522322  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
129502349  mitogen-activated protein kinase 3-like [KO:K04371] [EC:2.7.11.24]
129507918  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
129519082  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
129496789  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
129498637  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
129507069  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
129513452  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
129520803  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
129522073  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
129508823  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129495892  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129499851  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
129517633  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
129514778  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
129494520  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
129494269  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
129519569  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
129522106  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
129513852  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
129498792  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
129501980  KCNJ6; G protein-activated inward rectifier potassium channel 2 isoform X1 [KO:K05000]
129515270  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
129497495  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
129511116  POMC; pro-opiomelanocortin [KO:K05228]
129499790  OPRM1; LOW QUALITY PROTEIN: mu-type opioid receptor [KO:K04215]
129522341  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
129500644  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
129496894  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
129504276  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
129497646  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
129500550  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
129521608  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
129505465  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
129512495  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
129495972  CALM1; calmodulin-1 [KO:K02183]
129497741  CALML6; calmodulin-like protein 6 [KO:K02183]
129506414  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
129500769  CALM3; calmodulin-3 [KO:K02183]
129511712  CALM2; calmodulin-2 isoform X1 [KO:K02183]
129513685  calmodulin-like protein 3 [KO:K02183]
129513765  CALML5; calmodulin-like protein 5 [KO:K02183]
129515953  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
129500488  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
npo04010  MAPK signaling pathway
npo04020  Calcium signaling pathway
npo04151  PI3K-Akt signaling pathway
npo04270  Vascular smooth muscle contraction
npo04727  GABAergic synapse
npo04913  Ovarian steroidogenesis
KO pathway
ko04915   
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