KEGG   PATHWAY: llv04915
Entry
llv04915                    Pathway                                
Name
Estrogen signaling pathway - Lutra lutra (Eurasian river otter)
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
llv04915  Estrogen signaling pathway
llv04915

Other DBs
GO: 0030520
Organism
Lutra lutra (Eurasian river otter) [GN:llv]
Gene
125102786  estrogen receptor isoform X1 [KO:K08550]
125105364  estrogen receptor beta [KO:K08551]
125092011  heat shock protein HSP 90-alpha-like [KO:K04079]
125101710  heat shock protein HSP 90-beta [KO:K04079]
125104755  heat shock protein HSP 90-alpha [KO:K04079]
125098939  heat shock protein HSP 90-alpha-like [KO:K04079]
125107935  endoplasmin [KO:K09487]
125102682  peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
125106257  peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
125107574  heat shock cognate 71 kDa protein-like [KO:K03283]
125100538  heat shock cognate 71 kDa protein [KO:K03283]
125100679  heat shock cognate 71 kDa protein-like [KO:K03283]
125108856  heat shock cognate 71 kDa protein-like [KO:K03283]
125092981  heat shock cognate 71 kDa protein-like [KO:K03283]
125093086  heat shock cognate 71 kDa protein-like [KO:K03283]
125078422  heat shock cognate 71 kDa protein [KO:K03283]
125102166  heat shock 70 kDa protein 1 [KO:K03283]
125102167  heat shock 70 kDa protein 1-like [KO:K03283]
125094337  heat shock cognate 71 kDa protein-like [KO:K03283]
125078931  heat shock cognate 71 kDa protein-like [KO:K03283]
125102986  heat shock cognate 71 kDa protein-like [KO:K03283]
125108503  LOW QUALITY PROTEIN: nuclear receptor coactivator 1-like [KO:K09101] [EC:2.3.1.48]
125098982  nuclear receptor coactivator 2 isoform X1 [KO:K11255]
125109465  LOW QUALITY PROTEIN: nuclear receptor coactivator 3-like [KO:K11256] [EC:2.3.1.48]
125081686  apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
125097924  receptor-binding cancer antigen expressed on SiSo cells isoform X1 [KO:K22455]
125107797  keratin, type I cytoskeletal 18 [KO:K07604]
125086668  keratin, type I cytoskeletal 9-like [KO:K07604]
125087258  keratin, type I cuticular Ha5 [KO:K07604]
125087291  keratin, type I cytoskeletal 10-like isoform X1 [KO:K07604]
125087292  keratin, type I cytoskeletal 12-like [KO:K07604]
125087293  keratin, type I cytoskeletal 39-like [KO:K07604]
125087294  keratin, type I cytoskeletal 20-like [KO:K07604]
125087295  keratin, type I cytoskeletal 23-like [KO:K07604]
125087296  keratin, type I cytoskeletal 40 [KO:K07604]
125087347  keratin, type I cuticular Ha8-like [KO:K07604]
125087348  keratin, type I cuticular Ha2-like [KO:K07604]
125087349  keratin, type I cuticular Ha7-like [KO:K07604]
125087350  keratin, type I cuticular Ha7-like [KO:K07604]
125087351  keratin, type I cuticular Ha1 [KO:K07604]
125087352  keratin, type I cuticular Ha3-I [KO:K07604]
125087353  keratin, type I cuticular Ha1-like [KO:K07604]
125087354  keratin, type I cuticular Ha3-II-like [KO:K07604]
125087547  keratin, type I cytoskeletal 17 [KO:K07604]
125087548  keratin, type I cytoskeletal 16 isoform X1 [KO:K07604]
125087549  keratin, type I cytoskeletal 42 [KO:K07604]
125087551  keratin, type I cytoskeletal 19 [KO:K07604]
125087692  keratin, type I cytoskeletal 28 isoform X1 [KO:K07604]
125087694  keratin, type I cytoskeletal 26-like [KO:K07604]
125087695  keratin, type I cytoskeletal 25 [KO:K07604]
125087791  keratin, type I cuticular Ha6 [KO:K07604]
125087792  keratin, type I cytoskeletal 15 [KO:K07604]
125087793  keratin, type I cytoskeletal 13-like [KO:K07604]
125104175  keratin, type I cytoskeletal 18-like [KO:K07604]
125088075  keratin, type I cytoskeletal 24-like [KO:K07604]
125078652  cathepsin D isoform X1 [KO:K01379] [EC:3.4.23.5]
125109304  LOW QUALITY PROTEIN: protein GREB1-like [KO:K27477]
125097613  trefoil factor 1-like [KO:K22456]
125080136  progesterone receptor-like [KO:K08556]
125087842  retinoic acid receptor alpha isoform X1 [KO:K08527]
125105343  protein c-Fos [KO:K04379]
125098159  transcription factor Jun [KO:K04448]
125106436  transcription factor Sp1 [KO:K04684]
125090159  G-protein coupled estrogen receptor 1 [KO:K04246]
125108178  neuroendocrine secretory protein 55 [KO:K04632]
125108177  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like [KO:K04632]
125108930  proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
125089554  72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
125109962  matrix metalloproteinase-9 isoform X1 [KO:K01403] [EC:3.4.24.35]
125100868  proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
125081029  adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
125099871  adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
125108687  adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
125104720  adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
125103305  adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
125106490  adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
125088705  adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
125098951  adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
125091072  adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
125083608  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
125097539  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
125095039  cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
125095761  cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
125106338  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
125083953  cyclic AMP-responsive element-binding protein 3-like [KO:K09048]
125085653  cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
125086626  cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
125079521  cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
125080714  cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
125080867  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
125101524  cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
125080419  epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
125086356  SHC-transforming protein 1 isoform X1 [KO:K06279]
125087478  SHC-transforming protein 2 isoform X1 [KO:K17447]
125083737  SHC-transforming protein 3 [KO:K17448]
125105042  SHC-transforming protein 4 isoform X1 [KO:K17449]
125087106  growth factor receptor-bound protein 2 [KO:K04364]
125109653  LOW QUALITY PROTEIN: son of sevenless homolog 1-like [KO:K03099]
125104149  son of sevenless homolog 2 isoform X1 [KO:K03099]
125078621  GTPase HRas isoform X1 [KO:K02833]
125106241  GTPase KRas isoform X1 [KO:K07827]
125098043  GTPase NRas [KO:K07828]
125108469  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
125105594  dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
125086704  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
125081690  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
125090203  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
125100627  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
125103868  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
125096824  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
125099801  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
125082268  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
125097558  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
125086439  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125104283  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
125089561  RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125083887  gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
125102131  gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
125079775  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
125081463  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
125097631  guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
125089264  guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
125095746  G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
125094348  G protein-activated inward rectifier potassium channel 2 [KO:K05000]
125085485  G protein-activated inward rectifier potassium channel 3 [KO:K05002]
125079942  G protein-activated inward rectifier potassium channel 4 [KO:K04999]
125109273  pro-opiomelanocortin [KO:K05228]
125102176  mu-type opioid receptor isoform X1 [KO:K04215]
125078754  protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
125083151  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
125108695  LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like [KO:K05858] [EC:3.1.4.11]
125108926  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
125110237  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
125105190  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
125109360  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
125107116  inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
125103123  inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
125099896  calmodulin-1-like [KO:K02183]
125107709  calmodulin-like protein 3 [KO:K02183]
125092830  calmodulin-1 [KO:K02183]
125109105  calmodulin-1 [KO:K02183]
125104272  calmodulin-like protein 4 isoform X1 [KO:K02183]
125104293  calmodulin-1 [KO:K02183]
125097034  calmodulin-like protein 6 [KO:K02183]
125097532  calmodulin-1-like [KO:K02183]
125089454  calmodulin-1 [KO:K02183]
125081326  nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
125103220  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
llv04010  MAPK signaling pathway
llv04020  Calcium signaling pathway
llv04151  PI3K-Akt signaling pathway
llv04270  Vascular smooth muscle contraction
llv04727  GABAergic synapse
llv04913  Ovarian steroidogenesis
KO pathway
ko04915   
LinkDB

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