KEGG   PATHWAY: rfq04915
Entry
rfq04915                    Pathway                                
Name
Estrogen signaling pathway - Rhinolophus ferrumequinum (greater horseshoe bat)
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
rfq04915  Estrogen signaling pathway
rfq04915

Other DBs
GO: 0030520
Organism
Rhinolophus ferrumequinum (greater horseshoe bat) [GN:rfq]
Gene
117011845  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
117012187  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
117012305  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
117012438  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
117012484  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
117012667  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
117012708  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
117013127  KRT16; keratin, type I cytoskeletal 16 [KO:K07604]
117013128  [KO:K07604]
117013129  KRT17; keratin, type I cytoskeletal 17 [KO:K07604]
117013130  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
117013131  [KO:K07604]
117013296  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
117013301  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
117013439  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
117013463  [KO:K07604]
117013472  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
117013473  [KO:K07604]
117013481  [KO:K07604]
117013490  [KO:K07604]
117013491  [KO:K07604]
117013492  [KO:K07604]
117013525  KRT24; keratin, type I cytoskeletal 24 isoform X1 [KO:K07604]
117013534  [KO:K07604]
117013536  KRT28; keratin, type I cytoskeletal 28 [KO:K07604]
117013546  [KO:K02183]
117013549  [KO:K07604]
117013593  [KO:K07604]
117013636  [KO:K02833]
117013642  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
117013718  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
117013865  KRT12; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 12 [KO:K07604]
117014108  [KO:K07604]
117014109  KRT10; keratin, type I cytoskeletal 10 isoform X1 [KO:K07604]
117014645  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
117014672  NRAS; GTPase NRas [KO:K07828]
117014851  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
117015156  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
117015251  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
117015705  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
117015708  [KO:K04632]
117015819  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
117015870  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
117015877  OPRM1; mu-type opioid receptor isoform X1 [KO:K04215]
117015911  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
117015942  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
117016261  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
117016417  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
117016491  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
117016991  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
117017211  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
117017248  HSPA8; heat shock cognate 71 kDa protein isoform X1 [KO:K03283]
117017296  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
117017573  [KO:K22455]
117017906  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
117018010  [KO:K03283]
117018018  [KO:K03283]
117018025  HSPA1L; heat shock 70 kDa protein 1-like [KO:K03283]
117018030  [KO:K03283]
117018063  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
117018217  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
117018458  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117019182  [KO:K02183]
117019237  [KO:K02183]
117019474  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
117019993  [KO:K03283]
117020159  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 [KO:K04615]
117020173  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
117020443  GRM1; metabotropic glutamate receptor 1 isoform X1 [KO:K04603]
117020528  ESR1; estrogen receptor [KO:K08550]
117020871  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
117022805  ESR2; estrogen receptor beta [KO:K08551]
117022841  CALM1; calmodulin-1 [KO:K02183]
117022939  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
117022968  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
117023049  [KO:K04079]
117023064  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
117023560  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117023566  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
117023744  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
117024110  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
117024158  FOS; proto-oncogene c-Fos [KO:K04379]
117024169  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
117024531  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
117025090  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
117025697  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
117025773  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
117026238  KCNJ3; G protein-activated inward rectifier potassium channel 1 [KO:K04997]
117026472  CALML6; calmodulin-like protein 6 [KO:K02183]
117027001  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
117027160  [KO:K02649]
117027175  JUN; transcription factor AP-1 [KO:K04448]
117027443  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
117027721  [KO:K03283]
117028134  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
117028303  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
117028359  SP1; transcription factor Sp1 [KO:K04684]
117028439  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
117028695  HSP90B1; endoplasmin [KO:K09487]
117028978  KRAS; GTPase KRas isoform X1 [KO:K07827]
117029137  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
117029462  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
117029835  HRAS; LOW QUALITY PROTEIN: GTPase HRas [KO:K02833]
117030562  PGR; progesterone receptor isoform X1 [KO:K08556]
117030592  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
117030619  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
117031053  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
117031331  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
117031476  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
117031869  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
117031898  SHC3; SHC-transforming protein 3 [KO:K17448]
117032281  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
117032481  [KO:K03283]
117032677  GREB1; protein GREB1 [KO:K27477]
117032776  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
117032856  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
117032869  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
117033010  CALM2; calmodulin-2 [KO:K02183]
117033055  POMC; pro-opiomelanocortin [KO:K05228]
117033382  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
117033603  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
117033942  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
117034060  EBAG9; receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
117034378  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
117034411  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
117034856  CALM3; calmodulin-3 [KO:K02183]
117035064  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
117035083  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
117035241  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
117035383  KCNJ6; G protein-activated inward rectifier potassium channel 2 isoform X1 [KO:K05000]
117036086  [KO:K04079]
117036905  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
117037029  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
117037173  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
117037221  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
117037259  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
117037633  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
117037860  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
117037901  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
117037962  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
117038261  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
117038651  [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
rfq04010  MAPK signaling pathway
rfq04020  Calcium signaling pathway
rfq04151  PI3K-Akt signaling pathway
rfq04270  Vascular smooth muscle contraction
rfq04727  GABAergic synapse
rfq04913  Ovarian steroidogenesis
KO pathway
ko04915   

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