KEGG   PATHWAY: ray04915
ray04915                    Pathway                                

Estrogen signaling pathway - Rousettus aegyptiacus (Egyptian rousette)
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.
Organismal Systems; Endocrine system
Pathway map
ray04915  Estrogen signaling pathway

Other DBs
GO: 0030520
Rousettus aegyptiacus (Egyptian rousette) [GN:ray]
107513028  ESR1; estrogen receptor isoform X1 [KO:K08550]
107509325  ESR2; estrogen receptor beta isoform X1 [KO:K08551]
107501998  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
107521381  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
107501143  HSP90B1; endoplasmin [KO:K09487]
107502693  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 isoform X1 [KO:K09571] [EC:]
107497879  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 isoform X1 [KO:K09571] [EC:]
107503644  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
107498470  LOW QUALITY PROTEIN: heat shock 70 kDa protein 1-like [KO:K03283]
107498471  heat shock 70 kDa protein 1-like isoform X1 [KO:K03283]
107509320  HSPA2; heat shock-related 70 kDa protein 2 [KO:K03283]
107498469  HSPA1A; heat shock 70 kDa protein 1A [KO:K03283]
107498504  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:]
107514828  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
107498277  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:]
107503915  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
107517839  EBAG9; receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
107513759  keratin, type I cuticular Ha7-like [KO:K07604]
107513760  keratin, type I cytoskeletal 42 [KO:K07604]
107513768  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
107513769  KRT28; keratin, type I cytoskeletal 28 [KO:K07604]
107513770  KRT10; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 10 [KO:K07604]
107513771  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
107513772  keratin, type I cytoskeletal 40-like [KO:K07604]
107513774  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
107513792  keratin, type I cuticular Ha7-like [KO:K07604]
107513793  KRT38; keratin, type I cuticular Ha8 [KO:K07604]
107513794  keratin, type I cytoskeletal 15 [KO:K07604]
107513795  keratin, type I cytoskeletal 13-like [KO:K07604]
107513796  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
107509837  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
107513868  KRT24; keratin, type I cytoskeletal 24 isoform X1 [KO:K07604]
107513869  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
107513870  KRT26; keratin, type I cytoskeletal 26 [KO:K07604]
107513871  keratin, type I cytoskeletal 27 isoform X1 [KO:K07604]
107513872  KRT33A; keratin, type I cuticular Ha3-I [KO:K07604]
107513873  keratin, type I cuticular Ha3-I-like [KO:K07604]
107513874  keratin, type I cuticular Ha4 [KO:K07604]
107513875  keratin, type I cuticular Ha1 [KO:K07604]
107513876  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
107513877  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
107513878  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
107513879  keratin, type I cytoskeletal 14 [KO:K07604]
107513880  KRT16; keratin, type I cytoskeletal 16 [KO:K07604]
107513882  KRT17; keratin, type I cytoskeletal 17 [KO:K07604]
107513216  CTSD; cathepsin D [KO:K01379] [EC:]
107504647  PGR; progesterone receptor isoform X1 [KO:K08556]
107519111  TGFA; protransforming growth factor alpha [KO:K08774]
107520689  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
107498912  FOS; proto-oncogene c-Fos [KO:K04379]
107518352  JUN; transcription factor AP-1 [KO:K04448]
107509855  SP1; transcription factor Sp1 [KO:K04684]
107497376  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
107500068  neuroendocrine secretory protein 55-like [KO:K04632]
107500067  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
107512598  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:]
107499669  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:]
107514536  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:]
107521572  HBEGF; LOW QUALITY PROTEIN: proheparin-binding EGF-like growth factor [KO:K08523]
107512406  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:]
107502700  ADCY2; LOW QUALITY PROTEIN: adenylate cyclase type 2 [KO:K08042] [EC:]
107498506  ADCY3; LOW QUALITY PROTEIN: adenylate cyclase type 3 [KO:K08043] [EC:]
107498014  ADCY4; LOW QUALITY PROTEIN: adenylate cyclase type 4 [KO:K08044] [EC:]
107518038  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:]
107514224  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:]
107512248  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:]
107497689  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:]
107521680  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:]
107519437  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:]
107511590  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:]
107505169  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
107504977  ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
107500816  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
107509179  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
107502779  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
107511864  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
107510647  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
107499057  CREB3L2; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
107505683  CREB5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
107498439  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
107498193  EGFR; epidermal growth factor receptor [KO:K04361] [EC:]
107505474  SHC1; LOW QUALITY PROTEIN: SHC-transforming protein 1 [KO:K06279]
107512423  LOW QUALITY PROTEIN: SHC-transforming protein 1-like [KO:K06279]
107500961  SHC2; LOW QUALITY PROTEIN: SHC-transforming protein 2 [KO:K17447]
107504308  SHC3; LOW QUALITY PROTEIN: SHC-transforming protein 3 [KO:K17448]
107519965  SHC4; SHC-transforming protein 4 [KO:K17449]
107503781  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
107519446  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
107511436  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
107507127  HRAS; GTPase HRas isoform X1 [KO:K02833]
107497434  KRAS; GTPase KRas isoform X1 [KO:K07827]
107499847  NRAS; LOW QUALITY PROTEIN: GTPase NRas [KO:K07828]
107519729  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:]
107508942  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:]
107510634  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:]
107515836  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:]
107497830  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
107520152  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:]
107517828  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:]
107513958  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:]
107521668  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
107517899  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
107498704  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
107513978  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:]
107521783  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:]
107498395  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:]
107511694  GABBR2; LOW QUALITY PROTEIN: gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
107498080  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
107516134  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
107518173  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
107513376  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
107499654  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
107521176  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
107499288  KCNJ6; G protein-activated inward rectifier potassium channel 2 isoform X1 [KO:K05000]
107507932  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
107507814  KCNJ5; G protein-activated inward rectifier potassium channel 4 isoform X1 [KO:K04999]
107498502  POMC; pro-opiomelanocortin [KO:K05228]
107516517  OPRM1; mu-type opioid receptor isoform X1 [KO:K04215]
107516555  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:]
107517194  GNAQ; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
107506114  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:]
107519930  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:]
107497081  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:]
107514464  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:]
107504134  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
107497427  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
107511965  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
107509556  CALM2; calmodulin [KO:K02183]
107508927  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
107515457  CALM1; calmodulin [KO:K02183]
107516034  CALM3; calmodulin [KO:K02183]
107501627  calmodulin-like protein 5 [KO:K02183]
107520319  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:]
107518526  GRM1; metabotropic glutamate receptor 1 isoform X1 [KO:K04603]
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
Zhang D, Trudeau VL
Integration of membrane and nuclear estrogen receptor signaling.
Comp Biochem Physiol A Mol Integr Physiol 144:306-15 (2006)
Roepke TA, Qiu J, Bosch MA, Ronnekleiv OK, Kelly MJ
Cross-talk between membrane-initiated and nuclear-initiated oestrogen signalling in the hypothalamus.
J Neuroendocrinol 21:263-70 (2009)
McCarthy MM
The two faces of estradiol: effects on the developing brain.
Neuroscientist 15:599-610 (2009)
Kelly MJ, Ronnekleiv OK
Membrane-initiated estrogen signaling in hypothalamic neurons.
Mol Cell Endocrinol 290:14-23 (2008)
Kelly MJ, Qiu J, Ronnekleiv OK
Estrogen signaling in the hypothalamus.
Vitam Horm 71:123-45 (2005)
Raz L, Khan MM, Mahesh VB, Vadlamudi RK, Brann DW
Rapid estrogen signaling in the brain.
Neurosignals 16:140-53 (2008)
Malyala A, Kelly MJ, Ronnekleiv OK
Estrogen modulation of hypothalamic neurons: activation of multiple signaling pathways and gene expression changes.
Steroids 70:397-406 (2005)
Qiu J, Bosch MA, Tobias SC, Grandy DK, Scanlan TS, Ronnekleiv OK, Kelly MJ
Rapid signaling of estrogen in hypothalamic neurons involves a novel G-protein-coupled estrogen receptor that activates protein kinase C.
J Neurosci 23:9529-40 (2003)
Kelly MJ, Qiu J, Ronnekleiv OK
Estrogen modulation of G-protein-coupled receptor activation of potassium channels in the central nervous system.
Ann N Y Acad Sci 1007:6-16 (2003)
Meyer MR, Haas E, Prossnitz ER, Barton M
Non-genomic regulation of vascular cell function and growth by estrogen.
Mol Cell Endocrinol 308:9-16 (2009)
do Nascimento GR, Barros YV, Wells AK, Khalil RA
Research into Specific Modulators of Vascular Sex Hormone Receptors in the Management of Postmenopausal Cardiovascular Disease.
Curr Hypertens Rev 5:283-306 (2009)
Bjornstrom L, Sjoberg M
Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes.
Mol Endocrinol 19:833-42 (2005)
Manavathi B, Kumar R
Steering estrogen signals from the plasma membrane to the nucleus: two sides of the coin.
J Cell Physiol 207:594-604 (2006)
Prossnitz ER, Barton M
The G-protein-coupled estrogen receptor GPER in health and disease.
Nat Rev Endocrinol 7:715-26 (2011)
Meyer MR, Prossnitz ER, Barton M
The G protein-coupled estrogen receptor GPER/GPR30 as a regulator of cardiovascular function.
Vascul Pharmacol 55:17-25 (2011)
Maggiolini M, Picard D
The unfolding stories of GPR30, a new membrane-bound estrogen receptor.
J Endocrinol 204:105-14 (2010)
Prossnitz ER, Maggiolini M
Mechanisms of estrogen signaling and gene expression via GPR30.
Mol Cell Endocrinol 308:32-8 (2009)
Kelly MJ, Qiu J, Wagner EJ, Ronnekleiv OK
Rapid effects of estrogen on G protein-coupled receptor activation of potassium channels in the central nervous system (CNS).
J Steroid Biochem Mol Biol 83:187-93 (2002)
Paech K, Webb P, Kuiper GG, Nilsson S, Gustafsson J, Kushner PJ, Scanlan TS
Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites.
Science 277:1508-10 (1997)
Razandi M, Pedram A, Park ST, Levin ER
Proximal events in signaling by plasma membrane estrogen receptors.
J Biol Chem 278:2701-12 (2003)
Roepke TA, Xue C, Bosch MA, Scanlan TS, Kelly MJ, Ronnekleiv OK
Genes associated with membrane-initiated signaling of estrogen and energy homeostasis.
Endocrinology 149:6113-24 (2008)
Thomas C, Gustafsson JA
The different roles of ER subtypes in cancer biology and therapy.
Nat Rev Cancer 11:597-608 (2011)
ray04010  MAPK signaling pathway
ray04020  Calcium signaling pathway
ray04151  PI3K-Akt signaling pathway
ray04270  Vascular smooth muscle contraction
ray04727  GABAergic synapse
ray04913  Ovarian steroidogenesis
KO pathway

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