KEGG   PATHWAY: pvp04915
Entry
pvp04915                    Pathway                                
Name
Estrogen signaling pathway - Pteropus vampyrus (large 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
pvp04915  Estrogen signaling pathway
pvp04915

Other DBs
GO: 0030520
Organism
Pteropus vampyrus (large flying fox) [GN:pvp]
Gene
105293851  ESR1; estrogen receptor [KO:K08550]
105308555  ESR2; estrogen receptor beta isoform X2 [KO:K08551]
105288497  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
105299280  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
105310743  HSP90B1; endoplasmin [KO:K09487]
105297271  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
105301051  peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
105305304  heat shock 70 kDa protein 1-like [KO:K03283]
105307477  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
105289767  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
105295104  NCOA2; nuclear receptor coactivator 2 [KO:K11255]
105298182  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
105292717  BCL2; apoptosis regulator Bcl-2 isoform X2 [KO:K02161]
105292228  EBAG9; receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
105306317  keratin, type I cytoskeletal 14 [KO:K07604]
105306318  keratin, type I cytoskeletal 17 isoform X2 [KO:K07604]
105306319  KRT15; keratin, type I cytoskeletal 15 [KO:K07604]
105306320  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
105306321  KRT13; keratin, type I cytoskeletal 13 [KO:K07604]
105306322  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
105306323  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
105306324  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
105306325  LOW QUALITY PROTEIN: keratin, type I cuticular Ha8-like [KO:K07604]
105306326  keratin, type I cuticular Ha7-like [KO:K07604]
105306328  KRT34; keratin, type I cuticular Ha4 [KO:K07604]
105306329  keratin, type I cuticular Ha7-like [KO:K07604]
105306330  keratin, type I cuticular Ha3-I [KO:K07604]
105306340  keratin, type I cytoskeletal 42 [KO:K07604]
105307531  KRT24; keratin, type I cytoskeletal 24 isoform X1 [KO:K07604]
105307532  KRT26; keratin, type I cytoskeletal 26 [KO:K07604]
105307533  keratin, type I cytoskeletal 27 isoform X1 [KO:K07604]
105307534  KRT10; keratin, type I cytoskeletal 10 isoform X1 [KO:K07604]
105307535  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
105307536  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
105307537  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
105307549  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
105307550  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 28 [KO:K07604]
105307551  keratin, type I cytoskeletal 20 [KO:K07604]
105307552  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
105302673  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
105310491  keratin, type I cuticular Ha3-I-like [KO:K07604]
105299530  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
105311653  cathepsin D-like [KO:K01379] [EC:3.4.23.5]
105311654  uncharacterized protein LOC105311654 [KO:K01379] [EC:3.4.23.5]
105295462  GREB1; protein GREB1 [KO:K27477]
105300577  TFF1; trefoil factor 1 isoform X2 [KO:K22456]
105298271  PGR; progesterone receptor [KO:K08556]
105295757  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
105307523  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
105299213  FOS; proto-oncogene c-Fos [KO:K04379]
105303436  JUN; transcription factor AP-1 [KO:K04448]
105302655  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
105304462  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
105296083  neuroendocrine secretory protein 55-like [KO:K04632]
105296513  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
105292047  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
105298192  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
105306966  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
105308299  adenylate cyclase type 1-like [KO:K08041] [EC:4.6.1.1]
105299581  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
105289813  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
105309400  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
105288850  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
105297518  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
105292087  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
105301250  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
105303095  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
105289063  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105308501  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
105298404  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
105290195  ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
105298070  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105296460  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
105306745  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
105290070  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
105306466  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
105291624  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
105293217  cyclic AMP-responsive element-binding protein 5 [KO:K09047]
105305286  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
105306141  epidermal growth factor receptor-like [KO:K04361] [EC:2.7.10.1]
105296379  SHC1; SHC-transforming protein 1 isoform X3 [KO:K06279]
105302278  SHC2; SHC-transforming protein 2 [KO:K17447]
105300265  SHC3; SHC-transforming protein 3 [KO:K17448]
105288811  SHC4; SHC-transforming protein 4 [KO:K17449]
105293353  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
105292949  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
105309535  SOS2; son of sevenless homolog 2 [KO:K03099]
105305933  HRAS; GTPase HRas isoform X1 [KO:K02833]
105294059  KRAS; GTPase KRas isoform X2 [KO:K07827]
105296550  NRAS; GTPase NRas isoform X1 [KO:K07828]
105299021  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105309827  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
105306744  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105289326  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
105304566  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
105307215  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105307575  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105308956  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
105296605  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105297140  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
105299371  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
105303899  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105300159  RAC-beta serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
105298702  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105296286  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
105308164  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X2 [KO:K04615]
105297202  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
105295155  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
105295517  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
105292074  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
105291464  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
105295807  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
105300718  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
105306042  KCNJ5; G protein-activated inward rectifier potassium channel 4 isoform X2 [KO:K04999]
105289810  POMC; pro-opiomelanocortin [KO:K05228]
105293834  OPRM1; mu-type opioid receptor isoform X2 [KO:K04215]
105304348  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
105302452  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
105297846  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
105288781  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
105298737  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
105299444  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
105295171  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
105294112  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
105301042  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
105297322  CALM3; calmodulin-3 [KO:K02183]
105290127  CALM1; calmodulin-1 [KO:K02183]
105299180  calmodulin [KO:K02183]
105292913  CALM2; calmodulin-2 isoform X1 [KO:K02183]
105309689  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
105303606  CALML6; calmodulin-like protein 6 [KO:K02183]
105303769  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
105289441  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
pvp04010  MAPK signaling pathway
pvp04020  Calcium signaling pathway
pvp04151  PI3K-Akt signaling pathway
pvp04270  Vascular smooth muscle contraction
pvp04727  GABAergic synapse
pvp04913  Ovarian steroidogenesis
KO pathway
ko04915   
LinkDB

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