KEGG   PATHWAY: phas04915
Entry
phas04915                   Pathway                                
Name
Estrogen signaling pathway - Phyllostomus hastatus (greater spear-nosed 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
phas04915  Estrogen signaling pathway
phas04915

Other DBs
GO: 0030520
Organism
Phyllostomus hastatus (greater spear-nosed bat) [GN:phas]
Gene
123821760  ESR1; estrogen receptor isoform X1 [KO:K08550]
123808514  ESR2; estrogen receptor beta [KO:K08551]
123821362  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
123808632  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
123810694  HSP90B1; endoplasmin [KO:K09487]
123813488  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 isoform X1 [KO:K09571] [EC:5.2.1.8]
123821923  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
123815187  LOW QUALITY PROTEIN: peptidyl-prolyl cis-trans isomerase FKBP5-like [KO:K09571] [EC:5.2.1.8]
123825909  peptidyl-prolyl cis-trans isomerase FKBP5-like [KO:K09571] [EC:5.2.1.8]
123810362  heat shock 70 kDa protein 1 [KO:K03283]
123810504  heat shock 70 kDa protein 1-like [KO:K03283]
123832579  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
123822444  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
123832898  NCOA2; nuclear receptor coactivator 2 [KO:K11255]
123814985  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
123826047  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
123833077  EBAG9; receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
123812657  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
123822838  keratin, type I cytoskeletal 18-like [KO:K07604]
123816712  KRT13; keratin, type I cytoskeletal 13 [KO:K07604]
123816714  KRT15; keratin, type I cytoskeletal 15 [KO:K07604]
123816930  keratin, type I cytoskeletal 16 [KO:K07604]
123816931  keratin, type I cytoskeletal 17 [KO:K07604]
123816932  keratin, type I cytoskeletal 42 isoform X1 [KO:K07604]
123817028  KRT24; keratin, type I cytoskeletal 24 [KO:K07604]
123817030  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
123817031  KRT27; keratin, type I cytoskeletal 27 [KO:K07604]
123817032  KRT28; keratin, type I cytoskeletal 28 [KO:K07604]
123817033  KRT26; keratin, type I cytoskeletal 26 [KO:K07604]
123817059  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
123817103  keratin, type I cuticular Ha7-like [KO:K07604]
123817104  keratin, type I cuticular Ha3-I [KO:K07604]
123817144  keratin, type I cuticular Ha3-I-like [KO:K07604]
123817150  keratin, type I cuticular Ha3-I-like [KO:K07604]
123817184  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
123817189  keratin, type I cuticular Ha1 [KO:K07604]
123817190  keratin, type I cuticular Ha7-like [KO:K07604]
123817191  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
123817297  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
123817309  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
123817325  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
123817452  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
123817484  KRT10; keratin, type I cytoskeletal 10 isoform X1 [KO:K07604]
123817487  keratin, type I cytoskeletal 14 [KO:K07604]
123817553  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
123817754  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
123807349  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
123822509  GREB1; protein GREB1 isoform X1 [KO:K27477]
123827941  TFF1; trefoil factor 1 [KO:K22456]
123805458  PGR; progesterone receptor [KO:K08556]
123811931  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
123817049  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
123808226  FOS; proto-oncogene c-Fos [KO:K04379]
123831409  JUN; transcription factor AP-1 [KO:K04448]
123812402  SP1; transcription factor Sp1 [KO:K04684]
123809637  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
123815116  neuroendocrine secretory protein 55-like [KO:K04632]
123815292  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
123814829  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
123806069  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
123815340  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
123806596  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
123811468  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
123824963  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
123822448  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
123820487  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
123826843  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
123812947  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
123805699  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
123833093  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
123807136  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
123828245  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
123816440  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
123828120  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
123808666  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
123816126  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
123804840  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
123819667  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
123813639  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
123829665  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
123810038  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
123811809  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
123810486  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
123811124  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
123804815  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
123813838  SHC2; SHC-transforming protein 2 [KO:K17447]
123815569  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
123808639  SHC4; SHC-transforming protein 4 [KO:K17449]
123817350  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
123811120  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
123807983  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
123807317  HRAS; GTPase HRas isoform X1 [KO:K02833]
123812406  KRAS; GTPase KRas isoform X1 [KO:K07827]
123804414  NRAS; GTPase NRas [KO:K07828]
123814364  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
123808110  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
123813640  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
123806569  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
123825523  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
123826750  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
123830565  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123831922  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123828291  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
123824527  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
123832298  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
123808608  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123823743  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123832297  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123820195  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
123810346  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
123804401  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
123811789  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
123830671  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
123805731  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
123813422  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
123827899  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
123820554  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
123832480  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
123822577  POMC; pro-opiomelanocortin [KO:K05228]
123821727  OPRM1; mu-type opioid receptor [KO:K04215]
123814537  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
123819693  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
123829335  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
123814755  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
123814917  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
123808665  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
123830469  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
123812354  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
123815944  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
123811737  CALM2; calmodulin-2 [KO:K02183]
123821009  calmodulin-1-like [KO:K02183]
123808002  CALM1; calmodulin-1 [KO:K02183]
123808036  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
123823025  CALM3; calmodulin-3 [KO:K02183]
123831226  CALML3; calmodulin-like protein 3 [KO:K02183]
123831240  calmodulin-like [KO:K02183]
123831845  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
123817951  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
123821691  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
phas04010  MAPK signaling pathway
phas04020  Calcium signaling pathway
phas04151  PI3K-Akt signaling pathway
phas04270  Vascular smooth muscle contraction
phas04727  GABAergic synapse
phas04913  Ovarian steroidogenesis
KO pathway
ko04915   
LinkDB

DBGET integrated database retrieval system