KEGG   PATHWAY: dnm04915
Entry
dnm04915                    Pathway                                
Name
Estrogen signaling pathway - Dasypus novemcinctus (nine-banded armadillo)
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
dnm04915  Estrogen signaling pathway
dnm04915

Other DBs
GO: 0030520
Organism
Dasypus novemcinctus (nine-banded armadillo) [GN:dnm]
Gene
101413338  ESR1; estrogen receptor isoform X1 [KO:K08550]
101415986  ESR2; estrogen receptor beta [KO:K08551]
101442872  heat shock protein HSP 90-alpha A2 [KO:K04079]
101438170  HSP90B1; endoplasmin [KO:K09487]
101418431  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
101428859  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
101420025  heat shock 70 kDa protein 1-like [KO:K03283]
101419752  heat shock-related 70 kDa protein 2-like [KO:K03283]
101411149  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
101414850  HSPA6; heat shock 70 kDa protein 6 [KO:K03283]
101432707  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
101411961  NCOA2; LOW QUALITY PROTEIN: nuclear receptor coactivator 2 [KO:K11255]
101416786  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
101445333  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
101440546  EBAG9; receptor-binding cancer antigen expressed on SiSo cells isoform X1 [KO:K22455]
101432065  keratin, type I cuticular Ha3-I-like [KO:K07604]
101432513  keratin, type I cuticular Ha3-I [KO:K07604]
101432954  keratin, type I cuticular Ha1 isoform X1 [KO:K07604]
101433395  KRT32; LOW QUALITY PROTEIN: keratin, type I cuticular Ha2 [KO:K07604]
101433831  KRT35; keratin, type I cuticular Ha5 isoform X1 [KO:K07604]
101434545  KRT13; keratin, type I cytoskeletal 13 [KO:K07604]
101434973  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
101436121  keratin, type I cytoskeletal 14 isoform X2 [KO:K07604]
101437233  KRT17; keratin, type I cytoskeletal 17 [KO:K07604]
101437665  keratin, type I cytoskeletal 42 [KO:K07604]
101445879  keratin, type I cuticular Ha3-I [KO:K07604]
101445679  KRT24; keratin, type I cytoskeletal 24 [KO:K07604]
101411224  KRT10; keratin, type I cytoskeletal 10 [KO:K07604]
101446326  LOW QUALITY PROTEIN: keratin, type I cuticular Ha8 [KO:K07604]
101447208  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 15 [KO:K07604]
101436807  KRT16; keratin, type I cytoskeletal 16 [KO:K07604]
101446143  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
101446595  keratin, type I cytoskeletal 26 isoform X1 [KO:K07604]
101447318  keratin, type I cytoskeletal 27 isoform X1 [KO:K07604]
101410803  keratin, type I cytoskeletal 28 [KO:K07604]
101411971  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
101412399  KRT23; keratin, type I cytoskeletal 23 isoform X1 [KO:K07604]
101413852  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
101414300  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
101414731  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
101412437  keratin, type I cytoskeletal 18 [KO:K07604]
101446770  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
101447366  keratin, type I cytoskeletal 18 [KO:K07604]
101423477  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
101441995  GREB1; protein GREB1 [KO:K27477]
101433244  TFF1; trefoil factor 1 [KO:K22456]
101428963  PGR; progesterone receptor [KO:K08556]
101418598  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
101433218  RARA; retinoic acid receptor alpha [KO:K08527]
101431782  FOS; proto-oncogene c-Fos [KO:K04379]
101412001  JUN; transcription factor AP-1 [KO:K04448]
101441960  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
101428152  neuroendocrine secretory protein 55-like [KO:K04632]
101426457  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
101442293  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
101438233  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
101419059  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
101411559  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
101411573  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
101419332  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
101417345  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
101442950  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
101427927  ADCY7; LOW QUALITY PROTEIN: adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
101422732  adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
101442901  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101413809  cAMP-dependent protein kinase type 2 [KO:K04345] [EC:2.7.11.11]
101423692  PRKACB; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
101445596  uncharacterized protein LOC101445596 [KO:K04345] [EC:2.7.11.11]
101434860  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
101414225  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
101410933  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101410879  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
101414637  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
101424631  CREB3L3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
101411890  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
101435604  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
101442310  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
101426399  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
101425452  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
105746538  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
101438260  SHC1; SHC-transforming protein 1 [KO:K06279]
101447321  SHC2; SHC-transforming protein 2 [KO:K17447]
101417480  SHC3; LOW QUALITY PROTEIN: SHC-transforming protein 3 [KO:K17448]
101422617  SHC4; SHC-transforming protein 4 [KO:K17449]
101422156  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
101433544  SOS2; son of sevenless homolog 2 [KO:K03099]
101419480  HRAS; GTPase HRas isoform X1 [KO:K02833]
101412233  KRAS; GTPase KRas isoform X4 [KO:K07827]
101430817  NRAS; GTPase NRas [KO:K07828]
101414240  LOW QUALITY PROTEIN: GTPase NRas-like [KO:K07828]
101421211  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101435268  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
101420546  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101430570  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101435742  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101444276  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101443761  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101426945  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101423744  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
101435351  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101433347  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101419022  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101428799  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101445813  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101418064  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 [KO:K04615]
101414190  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
101447951  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X2 [KO:K04630]
101441349  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
101426647  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
101423121  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
101424669  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
101424635  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
101447591  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
101428251  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
101413154  POMC; pro-opiomelanocortin [KO:K05228]
101437988  OPRM1; mu-type opioid receptor isoform X2 [KO:K04215]
101440758  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
111765858  guanine nucleotide-binding protein subunit alpha-11-like [KO:K04634]
101411610  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
101420315  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101419878  PLCB4; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
101413654  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X2 [KO:K05858] [EC:3.1.4.11]
101427179  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X2 [KO:K05858] [EC:3.1.4.11]
101429543  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
101423325  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101425999  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101430299  calmodulin-like [KO:K02183]
101416595  CALM2; calmodulin-2 [KO:K02183]
105744587  calmodulin-like [KO:K02183]
101417995  CALM1; calmodulin-1 [KO:K02183]
101437415  calmodulin-like protein 3 [KO:K02183]
101412843  CALML4; calmodulin-like protein 4 isoform X2 [KO:K02183]
101426965  CALM3; calmodulin-3 [KO:K02183]
101433723  NOS3; LOW QUALITY PROTEIN: nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
101447287  LOW QUALITY PROTEIN: metabotropic glutamate receptor 1 [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
dnm04010  MAPK signaling pathway
dnm04020  Calcium signaling pathway
dnm04151  PI3K-Akt signaling pathway
dnm04270  Vascular smooth muscle contraction
dnm04727  GABAergic synapse
dnm04913  Ovarian steroidogenesis
KO pathway
ko04915   
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