KEGG   PATHWAY: efus04915
Entry
efus04915                   Pathway                                
Name
Estrogen signaling pathway - Eptesicus fuscus (big brown 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
efus04915  Estrogen signaling pathway
efus04915

Other DBs
GO: 0030520
Organism
Eptesicus fuscus (big brown bat) [GN:efus]
Gene
103301582  ESR1; estrogen receptor [KO:K08550]
103283663  ESR2; estrogen receptor beta [KO:K08551]
103296621  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
103298031  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
103288948  HSP90B1; endoplasmin isoform X1 [KO:K09487]
103288021  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
103305001  LOW QUALITY PROTEIN: peptidyl-prolyl cis-trans isomerase FKBP5-like [KO:K09571] [EC:5.2.1.8]
103295516  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 isoform X1 [KO:K09571] [EC:5.2.1.8]
103300460  heat shock 70 kDa protein 1-like [KO:K03283]
103300527  heat shock 70 kDa protein 1-like [KO:K03283]
103304878  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
103301961  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
103300528  heat shock 70 kDa protein 1 [KO:K03283]
103297281  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
103305555  NCOA1; nuclear receptor coactivator 1 [KO:K09101] [EC:2.3.1.48]
103293952  NCOA2; nuclear receptor coactivator 2 [KO:K11255]
103304346  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
103303728  BCL2; apoptosis regulator Bcl-2 isoform X3 [KO:K02161]
103287672  EBAG9; receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
103293276  receptor-binding cancer antigen expressed on SiSo cells-like [KO:K22455]
103291026  keratin, type I cuticular Ha3-I [KO:K07604]
103291037  LOW QUALITY PROTEIN: keratin, type I cuticular Ha4-like [KO:K07604]
129147346  keratin, type I cuticular Ha7-like [KO:K07604]
103290965  KRT10; keratin, type I cytoskeletal 10 isoform X1 [KO:K07604]
129147006  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
103289126  keratin, type I cytoskeletal 26 [KO:K07604]
103289140  KRT27; keratin, type I cytoskeletal 27 isoform X2 [KO:K07604]
103289156  KRT28; keratin, type I cytoskeletal 28 [KO:K07604]
103289165  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
103289173  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
103289184  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
103289193  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
103289291  keratin, type I cuticular Ha3-I [KO:K07604]
103289300  keratin, type I cuticular Ha8-like [KO:K07604]
103289320  KRT15; keratin, type I cytoskeletal 15 [KO:K07604]
103289329  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
103289339  keratin, type I cytoskeletal 14 [KO:K07604]
103289345  KRT17; keratin, type I cytoskeletal 17 [KO:K07604]
103290975  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
103291048  keratin, type I cuticular Ha1 [KO:K07604]
103291111  KRT16; keratin, type I cytoskeletal 16 [KO:K07604]
103291120  keratin, type I cytoskeletal 42 [KO:K07604]
103289311  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
103291081  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
103291070  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
103291090  KRT13; keratin, type I cytoskeletal 13 [KO:K07604]
103291059  keratin, type I cuticular Ha7-like [KO:K07604]
103285552  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
103289116  KRT24; keratin, type I cytoskeletal 24 [KO:K07604]
103303253  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
103283173  GREB1; protein GREB1 [KO:K27477]
103289890  TFF1; trefoil factor 1 [KO:K22456]
103292998  PGR; progesterone receptor [KO:K08556]
103291446  TGFA; protransforming growth factor alpha [KO:K08774]
103289024  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
103283560  FOS; protein c-Fos [KO:K04379]
103284067  JUN; transcription factor Jun [KO:K04448]
103285347  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
103299211  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
103285782  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X4 [KO:K04632]
103285922  neuroendocrine secretory protein 55-like [KO:K04632]
103293309  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
103295886  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
103301946  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
103286010  HBEGF; proheparin-binding EGF-like growth factor isoform X2 [KO:K08523]
103303616  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
103305103  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
103305553  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
103301470  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
103298761  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
103285248  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
103295862  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
103302409  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
103286155  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
103300989  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X2 [KO:K04345] [EC:2.7.11.11]
103284158  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
103289363  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
103283488  ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
103288848  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
103286442  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
103290849  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
103294106  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
103298930  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
103294228  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
103291632  CREB5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
103300452  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
103294241  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
103298913  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
103294446  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
103297925  SHC3; SHC-transforming protein 3 [KO:K17448]
103287410  SHC4; SHC-transforming protein 4 [KO:K17449]
103298291  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
103283761  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
103305666  SOS1; son of sevenless homolog 1 [KO:K03099]
103302548  HRAS; GTPase HRas isoform X1 [KO:K02833]
103285154  KRAS; GTPase KRas isoform X1 [KO:K07827]
103291212  NRAS; GTPase NRas [KO:K07828]
103295757  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
103283794  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
103294231  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103287001  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
103296283  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103286747  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103296140  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103295411  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103299551  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103305161  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
103294784  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103284312  AKT2; RAC-beta serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
103301793  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103293483  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103286397  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
103300502  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 [KO:K04615]
103291154  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
103293295  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
103298642  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
103295848  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X3 [KO:K04534]
103283400  KCNJ3; G protein-activated inward rectifier potassium channel 1 [KO:K04997]
103289816  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
103297575  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
103286923  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
103305549  POMC; pro-opiomelanocortin [KO:K05228]
103297947  OPRM1; mu-type opioid receptor [KO:K04215]
103290422  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
129147180  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
103302044  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
103287505  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
103285666  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
103285667  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
103300420  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103285158  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103303043  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103292236  CALM1; calmodulin-1 isoform X2 [KO:K02183]
103298572  CALML5; calmodulin-like protein 5 [KO:K02183]
103304916  calmodulin-1-like [KO:K02183]
103305414  CALM2; calmodulin-2 [KO:K02183]
103297693  CALM3; calmodulin-3 isoform X1 [KO:K02183]
103298573  calmodulin-like protein 3 [KO:K02183]
103293186  calmodulin-1-like [KO:K02183]
129148572  calmodulin-1-like [KO:K02183]
103283955  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
129150189  CALML6; calmodulin-like protein 6 [KO:K02183]
103301781  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
103303960  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
efus04010  MAPK signaling pathway
efus04020  Calcium signaling pathway
efus04151  PI3K-Akt signaling pathway
efus04270  Vascular smooth muscle contraction
efus04727  GABAergic synapse
efus04913  Ovarian steroidogenesis
KO pathway
ko04915   
LinkDB

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