KEGG   PATHWAY: pale04915
Entry
pale04915                   Pathway                                
Name
Estrogen signaling pathway - Pteropus alecto (black flying fox)
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
pale04915  Estrogen signaling pathway
pale04915

Other DBs
GO: 0030520
Organism
Pteropus alecto (black flying fox) [GN:pale]
Gene
102877700  KRT26; keratin, type I cytoskeletal 26 [KO:K07604]
102877748  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
102877853  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
102877910  ESR1; estrogen receptor isoform X1 [KO:K08550]
102877919  [KO:K04634]
102877939  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
102877944  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
102878037  [KO:K07604]
102878198  KRT24; keratin, type I cytoskeletal 24 [KO:K07604]
102878281  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
102878324  ESR2; estrogen receptor beta isoform X2 [KO:K08551]
102878515  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
102878530  [KO:K07604]
102878791  [KO:K07604]
102878822  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
102878912  GRM1; metabotropic glutamate receptor 1 isoform X1 [KO:K04603]
102879034  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102879163  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102879238  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
102879289  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
102879337  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102879453  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102879632  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
102879945  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
102879956  SHC3; SHC-transforming protein 3 [KO:K17448]
102880048  HSPA1B; heat shock 70 kDa protein 1B [KO:K03283]
102880130  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
102880320  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102880632  [KO:K03283]
102881088  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
102881192  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
102881535  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
102881636  POMC; pro-opiomelanocortin [KO:K05228]
102881744  [KO:K02183]
102881783  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102882462  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
102882842  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
102882873  PGR; progesterone receptor isoform X1 [KO:K08556]
102882888  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
102883808  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
102883840  EBAG9; receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
102884106  [KO:K04632]
102884196  CALML6; calmodulin-like protein 6 [KO:K02183]
102884583  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
102884654  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X2 [KO:K04534]
102885144  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102885207  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
102885576  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
102885617  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
102885642  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
102885676  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
102885749  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102885781  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
102885950  NRAS; GTPase NRas isoform X2 [KO:K07828]
102885953  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
102885958  SHC2; SHC-transforming protein 2 [KO:K17447]
102886058  CALM1; calmodulin-1 [KO:K02183]
102886232  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
102886510  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
102886679  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102887497  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
102887662  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
102887850  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
102887985  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
102888198  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
102888325  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
102888600  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
102888926  SHC4; SHC-transforming protein 4 [KO:K17449]
102889014  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
102889156  HSP90B1; endoplasmin [KO:K09487]
102889227  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102889517  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
102889576  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102889597  SOS2; son of sevenless homolog 2 [KO:K03099]
102889764  [KO:K04632]
102890575  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
102890588  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
102891249  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
102891421  [KO:K07604]
102891428  FOS; proto-oncogene c-Fos [KO:K04379]
102891637  [KO:K02649]
102891661  [KO:K07604]
102891673  [KO:K02183]
102891897  [KO:K07604]
102892146  KRT15; keratin, type I cytoskeletal 15 [KO:K07604]
102892305  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
102892399  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
102892644  [KO:K07604]
102892705  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
102892785  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
102892892  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
102893109  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
102893127  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
102893265  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
102893345  OPRM1; mu-type opioid receptor isoform X2 [KO:K04215]
102893377  [KO:K07604]
102893439  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102893495  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102893625  [KO:K07604]
102893869  [KO:K07604]
102893956  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
102894100  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
102894109  [KO:K07604]
102894226  CALM2; calmodulin-2 isoform X1 [KO:K02183]
102894443  SHC1; LOW QUALITY PROTEIN: SHC-transforming protein 1 [KO:K06279]
102894633  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
102894982  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102895390  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102895417  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
102895590  KRAS; GTPase KRas isoform X1 [KO:K07827]
102896121  JUN; transcription factor AP-1 [KO:K04448]
102896270  HRAS; GTPase HRas isoform X3 [KO:K02833]
102896356  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
102896443  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
102896532  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
102896553  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
102896764  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
102896789  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
102897122  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102897152  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
102897273  CALM3; calmodulin-3 [KO:K02183]
102897318  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
102897397  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
102897495  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
102897638  KRT20; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 20 [KO:K07604]
102897884  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
102898128  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X3 [KO:K09049]
102898139  KRT10; keratin, type I cytoskeletal 10 [KO:K07604]
102898305  AKT2; LOW QUALITY PROTEIN: RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102898391  KRT28; keratin, type I cytoskeletal 28 [KO:K07604]
102898639  KRT27; keratin, type I cytoskeletal 27 [KO:K07604]
102898665  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
102898716  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
102898919  GREB1; protein GREB1 isoform X2 [KO:K27477]
107196005  TFF1; trefoil factor 1 [KO:K22456]
107196588  [KO:K07604]
112469030  [KO:K03283]
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
pale04010  MAPK signaling pathway
pale04020  Calcium signaling pathway
pale04151  PI3K-Akt signaling pathway
pale04270  Vascular smooth muscle contraction
pale04727  GABAergic synapse
pale04913  Ovarian steroidogenesis
KO pathway
ko04915   

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