KEGG   PATHWAY: hhv04915
Entry
hhv04915                    Pathway                                
Name
Estrogen signaling pathway - Hyaena hyaena (striped hyena)
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
hhv04915  Estrogen signaling pathway
hhv04915

Other DBs
GO: 0030520
Organism
Hyaena hyaena (striped hyena) [GN:hhv]
Gene
120237592  estrogen receptor-like [KO:K08550]
120222308  estrogen receptor [KO:K08550]
120238434  ESR2; estrogen receptor beta isoform X1 [KO:K08551]
120231200  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
120244587  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
120245709  HSP90B1; endoplasmin [KO:K09487]
120233823  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
120234483  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
120227766  heat shock 70 kDa protein 1 [KO:K03283]
120220580  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
120240081  heat shock cognate 71 kDa protein-like [KO:K03283]
120221892  heat shock 70 kDa protein 1-like [KO:K03283]
120221893  heat shock 70 kDa protein 1 [KO:K03283]
120221952  heat shock cognate 71 kDa protein-like [KO:K03283]
120241045  HSPA6; heat shock 70 kDa protein 6 [KO:K03283]
120249032  heat shock cognate 71 kDa protein-like [KO:K03283]
120235812  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
120235861  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
120243275  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
120245032  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
120246776  EBAG9; receptor-binding cancer antigen expressed on SiSo cells isoform X1 [KO:K22455]
120225061  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
120225062  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
120225065  KRT26; keratin, type I cytoskeletal 26 [KO:K07604]
120225066  KRT10; keratin, type I cytoskeletal 10 [KO:K07604]
120225067  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
120225068  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
120225069  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
120225071  KRT28; keratin, type I cytoskeletal 28 [KO:K07604]
120225072  KRT27; keratin, type I cytoskeletal 27 [KO:K07604]
120229041  KRT24; keratin, type I cytoskeletal 24 [KO:K07604]
120229164  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
120247276  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
120248384  keratin, type I cuticular Ha1-like isoform X1 [KO:K07604]
120248386  keratin, type I cuticular Ha1 [KO:K07604]
120248387  keratin, type I cuticular Ha3-II-like [KO:K07604]
120248400  keratin, type I cuticular Ha8-like [KO:K07604]
120248401  keratin, type I cuticular Ha8-like [KO:K07604]
120248403  keratin, type I cuticular Ha8-like [KO:K07604]
120248404  keratin, type I cuticular Ha3-I [KO:K07604]
120248406  KRT14; keratin, type I cytoskeletal 14 [KO:K07604]
120248414  keratin, type I cytoskeletal 42 [KO:K07604]
120248415  KRT16; keratin, type I cytoskeletal 16 [KO:K07604]
120248416  KRT17; keratin, type I cytoskeletal 17 [KO:K07604]
120248417  KRT15; keratin, type I cytoskeletal 15 isoform X1 [KO:K07604]
120248418  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
120248419  KRT13; keratin, type I cytoskeletal 13 [KO:K07604]
120248425  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
120248441  KRT9; keratin, type I cytoskeletal 9 [KO:K07604]
120248442  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
120248465  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
120225514  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
120231142  GREB1; protein GREB1 isoform X1 [KO:K27477]
120223596  PGR; progesterone receptor isoform X1 [KO:K08556]
120236624  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
120229003  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
120231952  FOS; proto-oncogene c-Fos [KO:K04379]
120236252  JUN; transcription factor AP-1 [KO:K04448]
120247236  SP1; transcription factor Sp1 [KO:K04684]
120227919  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
120234858  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
120234860  neuroendocrine secretory protein 55 [KO:K04632]
120228611  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
120238088  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
120243271  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
120245649  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
120238897  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
120225093  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
120235801  ADCY3; LOW QUALITY PROTEIN: adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
120247005  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
120237362  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
120223032  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
120238226  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
120221853  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
120236476  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
120241649  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
120245321  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
120220409  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
120243894  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
120235229  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
120232978  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
120228497  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
120221289  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
120221513  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
120242085  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
120230339  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
120221927  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
120238884  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
120244661  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
120242345  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
120237954  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
120220858  SHC4; SHC-transforming protein 4 [KO:K17449]
120228194  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
120220282  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
120244628  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
120223392  HRAS; GTPase HRas isoform X1 [KO:K02833]
120223531  KRAS; GTPase KRas [KO:K07827]
120243068  NRAS; GTPase NRas [KO:K07828]
120231327  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
120221655  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
120242086  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
120238830  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
120242212  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
120233608  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
120220979  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
120246696  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
120219997  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
120239233  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
120247089  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
120235277  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120244696  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120247774  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120233517  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
120226573  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
120229291  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
120244506  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
120245414  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
120232146  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
120223709  KCNJ3; G protein-activated inward rectifier potassium channel 1 [KO:K04997]
120230240  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
120241356  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
120237106  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
120235838  POMC; pro-opiomelanocortin [KO:K05228]
120233030  OPRM1; mu-type opioid receptor [KO:K04215]
120239415  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
120238451  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
120232253  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
120226357  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
120226638  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
120240178  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
120237135  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
120237482  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
120238181  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
120232098  CALM1; calmodulin-1 [KO:K02183]
120237182  calmodulin-like [KO:K02183]
120237195  calmodulin-like protein 3 [KO:K02183]
120241014  CALM2; calmodulin-2 [KO:K02183]
120221982  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
120241987  CALM3; calmodulin-3 isoform X1 [KO:K02183]
120242524  CALML6; calmodulin-like protein 6 [KO:K02183]
120230927  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
120231041  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
hhv04010  MAPK signaling pathway
hhv04020  Calcium signaling pathway
hhv04151  PI3K-Akt signaling pathway
hhv04270  Vascular smooth muscle contraction
hhv04727  GABAergic synapse
hhv04913  Ovarian steroidogenesis
KO pathway
ko04915   
LinkDB

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