KEGG   PATHWAY: setr04915
Entry
setr04915                   Pathway                                
Name
Estrogen signaling pathway - Suncus etruscus (white-toothed pygmy shrew)
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
setr04915  Estrogen signaling pathway
setr04915

Other DBs
GO: 0030520
Organism
Suncus etruscus (white-toothed pygmy shrew) [GN:setr]
Gene
125996530  ESR1; estrogen receptor [KO:K08550]
126003940  ESR2; estrogen receptor beta [KO:K08551]
126003543  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
125996306  LOW QUALITY PROTEIN: heat shock protein HSP 90-beta-like [KO:K04079]
125996555  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
126022286  HSP90B1; endoplasmin [KO:K09487]
125996364  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
126013732  heat shock cognate 71 kDa protein-like [KO:K03283]
125996185  heat shock 70 kDa protein 1-like [KO:K03283]
125996186  heat shock 70 kDa protein 1 [KO:K03283]
125996188  heat shock 70 kDa protein 1-like [KO:K03283]
126015401  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
126017986  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
126024055  NCOA1; nuclear receptor coactivator 1 [KO:K09101] [EC:2.3.1.48]
126020349  NCOA2; nuclear receptor coactivator 2 [KO:K11255]
125996161  LOW QUALITY PROTEIN: nuclear receptor coactivator 3-like [KO:K11256] [EC:2.3.1.48]
126019118  NCOA3; nuclear receptor coactivator 3 [KO:K11256] [EC:2.3.1.48]
126020600  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
126009477  EBAG9; receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
126022681  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
126017497  KRT10; keratin, type I cytoskeletal 10 isoform X1 [KO:K07604]
126017672  KRT24; keratin, type I cytoskeletal 24 [KO:K07604]
126017755  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
125999205  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
125999293  KRT20; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 20 [KO:K07604]
125999398  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
126017918  keratin, type I cytoskeletal 14 isoform X1 [KO:K07604]
126017955  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
126017959  KRT16; keratin, type I cytoskeletal 16 [KO:K07604]
126017970  keratin, type I cytoskeletal 26-like [KO:K07604]
126018045  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
126018076  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
126018085  keratin, type I cytoskeletal 28 [KO:K07604]
126018141  keratin, type I cytoskeletal 27 [KO:K07604]
126018151  KRT15; keratin, type I cytoskeletal 15 [KO:K07604]
126018207  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
126018218  keratin, type I cytoskeletal 42 [KO:K07604]
126018274  keratin, type I cuticular Ha8-like [KO:K07604]
126018284  KRT17; keratin, type I cytoskeletal 17 [KO:K07604]
126018292  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
126018436  keratin, type I cuticular Ha1-like [KO:K07604]
126000774  keratin, type I cuticular Ha1 [KO:K07604]
126000781  keratin, type I cuticular Ha7-like [KO:K07604]
126000790  keratin, type I cuticular Ha8-like [KO:K07604]
126000800  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
126000821  KRT9; keratin, type I cytoskeletal 9 [KO:K07604]
126019444  keratin, type I cuticular Ha4 [KO:K07604]
126019615  KRT13; keratin, type I cytoskeletal 13 [KO:K07604]
126019647  keratin, type I cuticular Ha3-I-like [KO:K07604]
126019064  CTSD; cathepsin D isoform X1 [KO:K01379] [EC:3.4.23.5]
126024092  GREB1; protein GREB1 [KO:K27477]
126015766  PGR; progesterone receptor [KO:K08556]
126024677  TGFA; protransforming growth factor alpha [KO:K08774]
126017691  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
126004042  FOS; protein c-Fos [KO:K04379]
126010979  JUN; transcription factor Jun [KO:K04448]
126022125  SP1; transcription factor Sp1 [KO:K04684]
126013317  GNAS; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
126013337  neuroendocrine secretory protein 55-like [KO:K04632]
126017330  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
126027090  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
126017313  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
126027052  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
126029834  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
126000769  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
126024026  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
126001049  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
126026247  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
126022668  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
126027080  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
125997104  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
126001221  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
126030328  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
126005939  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
126008959  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
126006901  LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-2-like [KO:K04450]
126009077  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
126006324  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
126029685  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
126012179  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
126009210  CREB3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3 [KO:K09048]
126017927  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
126020129  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
126020515  CREB5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
125996226  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
126013961  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
126020709  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
126030826  SHC2; SHC-transforming protein 2 [KO:K17447]
126003375  SHC3; SHC-transforming protein 3 [KO:K17448]
126020007  SHC4; SHC-transforming protein 4 [KO:K17449]
126003551  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
126023864  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
125999018  SOS2; son of sevenless homolog 2 [KO:K03099]
126019084  HRAS; GTPase HRas [KO:K02833]
126022823  KRAS; GTPase KRas isoform X1 [KO:K07827]
125997372  NRAS; GTPase NRas [KO:K07828]
125998044  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
126021920  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
126029670  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
126029893  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
126033704  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
126012035  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
126012036  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
126011501  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
126030200  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
126011086  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
126001552  PIK3R1; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
126013417  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
126033346  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
126028133  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
125996385  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 [KO:K04615]
126023323  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
126014071  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
126022872  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
125997317  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
126027101  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
126008767  KCNJ3; G protein-activated inward rectifier potassium channel 1 [KO:K04997]
126025599  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
126013957  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
126015697  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
126024045  POMC; pro-opiomelanocortin [KO:K05228]
125996440  OPRM1; mu-type opioid receptor [KO:K04215]
126013204  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
126003511  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
126017277  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
126024570  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
126017588  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
126018105  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
125998103  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
126022840  ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
125996360  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
126003621  CALM1; calmodulin-1 [KO:K02183]
126013297  calmodulin-like protein 3 [KO:K02183]
126013298  calmodulin-4-like [KO:K02183]
126023953  CALM2; calmodulin-2 [KO:K02183]
126015982  CALML4; calmodulin-like protein 4 [KO:K02183]
126031280  calmodulin-1-like [KO:K02183]
126001307  calmodulin-1-like [KO:K02183]
126028268  CALM3; calmodulin-3 [KO:K02183]
126021768  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
126031051  GRM1; 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
setr04010  MAPK signaling pathway
setr04020  Calcium signaling pathway
setr04151  PI3K-Akt signaling pathway
setr04270  Vascular smooth muscle contraction
setr04727  GABAergic synapse
setr04913  Ovarian steroidogenesis
KO pathway
ko04915   
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