KEGG   PATHWAY: pcad04915
Entry
pcad04915                   Pathway                                
Name
Estrogen signaling pathway - Physeter catodon (sperm whale)
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
pcad04915  Estrogen signaling pathway
pcad04915

Other DBs
GO: 0030520
Organism
Physeter catodon (sperm whale) [GN:pcad]
Gene
102978428  ESR1; estrogen receptor isoform X1 [KO:K08550]
102996150  ESR2; estrogen receptor beta [KO:K08551]
102980083  LOW QUALITY PROTEIN: heat shock protein HSP 90-alpha-like [KO:K04079]
102988570  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
102985047  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
102978403  LOW QUALITY PROTEIN: heat shock protein HSP 90-beta-like [KO:K04079]
102990733  HSP90B1; endoplasmin [KO:K09487]
102994891  peptidyl-prolyl cis-trans isomerase FKBP5-like [KO:K09571] [EC:5.2.1.8]
102987600  LOW QUALITY PROTEIN: peptidyl-prolyl cis-trans isomerase FKBP4-like [KO:K09571] [EC:5.2.1.8]
102993508  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
102987811  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
102982689  HSPA8; LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein [KO:K03283]
102974358  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
102994908  heat shock 70 kDa protein 1B [KO:K03283]
102995190  heat shock 70 kDa protein 1B [KO:K03283]
102995465  heat shock 70 kDa protein 1-like [KO:K03283]
102989030  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
102990601  HSPA6; LOW QUALITY PROTEIN: heat shock 70 kDa protein 6 [KO:K03283]
102983803  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
102973375  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
102986227  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
102994447  NCOA1; nuclear receptor coactivator 1 [KO:K09101] [EC:2.3.1.48]
102976427  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
102985044  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
102987942  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
102984035  EBAG9; receptor-binding cancer antigen expressed on SiSo cells isoform X1 [KO:K22455]
102976843  receptor-binding cancer antigen expressed on SiSo cells-like [KO:K22455]
112063612  receptor-binding cancer antigen expressed on SiSo cells-like [KO:K22455]
102995741  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 42-like [KO:K07604]
102974707  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 24 [KO:K07604]
102993501  KRT23; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 23 [KO:K07604]
102973192  KRT40; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 40 [KO:K07604]
102996290  LOW QUALITY PROTEIN: keratin, type I cuticular Ha2 [KO:K07604]
112066577  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 9 [KO:K07604]
102996008  KRT15; keratin, type I cytoskeletal 15 [KO:K07604]
102990369  keratin, type I cytoskeletal 14 [KO:K07604]
112066568  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
102990810  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 16 [KO:K07604]
102991846  keratin, type I cuticular Ha6 [KO:K07604]
102991095  KRT17; keratin, type I cytoskeletal 17 [KO:K07604]
102991388  keratin, type I cytoskeletal 13 [KO:K07604]
102992127  keratin, type I microfibrillar 48 kDa, component 8C-1-like [KO:K07604]
102994683  keratin, type I cytoskeletal 12 [KO:K07604]
102981005  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
102977115  keratin, type I cytoskeletal 18-like [KO:K07604]
102978791  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 18-like [KO:K07604]
102977235  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
102992117  protein GREB1 isoform X1 [KO:K27477]
102987147  PGR; progesterone receptor [KO:K08556]
102973542  TGFA; protransforming growth factor alpha isoform X4 [KO:K08774]
102981217  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
102982453  FOS; protein c-Fos [KO:K04379]
102975458  JUN; transcription factor Jun [KO:K04448]
102973166  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
102988721  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
102993267  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X2 [KO:K04632]
102987258  neuroendocrine secretory protein 55-like [KO:K04632]
102988341  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha-like [KO:K04632]
102983882  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
102973920  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
102977941  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
102994045  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
102981199  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
102991224  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
102989136  ADCY3; adenylate cyclase type 3 isoform X3 [KO:K08043] [EC:4.6.1.1]
102985820  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
102983319  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
102986152  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
102985075  ADCY7; adenylate cyclase type 7 isoform X4 [KO:K08047] [EC:4.6.1.1]
102975211  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
102995803  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
102981091  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
102995361  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
102989082  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
102974369  ATF2; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
102986837  LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-2-like [KO:K04450]
102984157  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
102994621  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X2 [KO:K09048]
102986078  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X3 [KO:K09048]
102987194  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
102975387  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
129391322  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
102985635  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X3 [KO:K09047]
102978131  ATF6B; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
102975467  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
102991486  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
102974315  SHC2; SHC-transforming protein 2 [KO:K17447]
102977456  SHC3; SHC-transforming protein 3 [KO:K17448]
102988652  SHC4; SHC-transforming protein 4 isoform X2 [KO:K17449]
114483947  growth factor receptor-bound protein 2 [KO:K04364]
102991639  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
102981677  LOW QUALITY PROTEIN: son of sevenless homolog 2-like [KO:K03099]
102978925  SOS2; LOW QUALITY PROTEIN: son of sevenless homolog 2 [KO:K03099]
102994715  HRAS; GTPase HRas isoform X2 [KO:K02833]
102977125  KRAS; GTPase KRas isoform X1 [KO:K07827]
102992439  LOW QUALITY PROTEIN: GTPase NRas-like [KO:K07828]
102982641  NRAS; LOW QUALITY PROTEIN: GTPase NRas [KO:K07828]
102987866  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
102992191  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102994150  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102984305  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102989074  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102986098  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102978952  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102977108  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102975555  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102991779  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102991192  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
102981524  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102976971  AKT3; RAC-gamma serine/threonine-protein kinase isoform X3 [KO:K04456] [EC:2.7.11.1]
102990087  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102993343  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X3 [KO:K04615]
102975766  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
102996618  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
102997009  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
102996666  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
102996655  KCNJ3; G protein-activated inward rectifier potassium channel 1 [KO:K04997]
102995845  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
102981203  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
102977820  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
102991057  POMC; pro-opiomelanocortin [KO:K05228]
102976521  OPRM1; mu-type opioid receptor isoform X1 [KO:K04215]
102984279  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
102979158  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
102995357  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X2 [KO:K05858] [EC:3.1.4.11]
102985636  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
102974165  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
102983015  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
102984842  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
102992034  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
102976671  CALM1; calmodulin-1 [KO:K02183]
102988232  calmodulin-alpha [KO:K02183]
102996886  calmodulin-1-like [KO:K02183]
102993731  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
102988309  CALM3; calmodulin-3 [KO:K02183]
102977506  uncharacterized protein LOC102977506 [KO:K02183]
129392645  neo-calmodulin-like [KO:K02183]
102985806  NOS3; nitric oxide synthase, endothelial isoform X2 [KO:K13242] [EC:1.14.13.39]
102978027  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
pcad04010  MAPK signaling pathway
pcad04020  Calcium signaling pathway
pcad04151  PI3K-Akt signaling pathway
pcad04270  Vascular smooth muscle contraction
pcad04727  GABAergic synapse
pcad04913  Ovarian steroidogenesis
KO pathway
ko04915   
LinkDB

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