KEGG   PATHWAY: pleu04915
Entry
pleu04915                   Pathway                                
Name
Estrogen signaling pathway - Peromyscus leucopus (white-footed mouse)
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
pleu04915  Estrogen signaling pathway
pleu04915

Other DBs
GO: 0030520
Organism
Peromyscus leucopus (white-footed mouse) [GN:pleu]
Gene
114707480  Esr1; estrogen receptor [KO:K08550]
114697733  Esr2; estrogen receptor beta [KO:K08551]
114691694  heat shock protein HSP 90-alpha-like [KO:K04079]
114686218  heat shock protein HSP 90-alpha-like [KO:K04079]
114707842  Hsp90ab1; heat shock protein HSP 90-beta [KO:K04079]
114703084  Hsp90aa1; heat shock protein HSP 90-alpha [KO:K04079]
114700616  Hsp90b1; endoplasmin [KO:K09487]
114695777  LOW QUALITY PROTEIN: endoplasmin-like [KO:K09487]
114706122  Fkbp5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
114701426  Fkbp4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
114701539  LOW QUALITY PROTEIN: peptidyl-prolyl cis-trans isomerase FKBP5-like [KO:K09571] [EC:5.2.1.8]
114691135  Hspa8; heat shock cognate 71 kDa protein [KO:K03283]
114686934  heat shock cognate 71 kDa protein-like [KO:K03283]
114690029  Hspa6; LOW QUALITY PROTEIN: heat shock 70 kDa protein 6 [KO:K03283]
114705867  Hspa1a; heat shock 70 kDa protein 1A [KO:K03283]
114705868  heat shock 70 kDa protein 1A [KO:K03283]
114705870  Hspa1l; heat shock 70 kDa protein 1-like [KO:K03283]
114697171  Ncoa1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
114690109  Ncoa2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
114692649  Ncoa3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
114702810  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
114692265  Ebag9; receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
114706915  Krt35; keratin, type I cuticular Ha5 [KO:K07604]
114706917  keratin, type I cuticular Ha2 [KO:K07604]
114706922  keratin, type I cytoskeletal 17 [KO:K07604]
114706925  keratin, type I cytoskeletal 42 [KO:K07604]
114706930  keratin, type I cytoskeletal 16 isoform X1 [KO:K07604]
114706932  Krt24; keratin, type I cytoskeletal 24 [KO:K07604]
114706933  Krt25; keratin, type I cytoskeletal 25 [KO:K07604]
114706935  Krt15; keratin, type I cytoskeletal 15 [KO:K07604]
114706937  Krt20; keratin, type I cytoskeletal 20 [KO:K07604]
114706938  Krt28; keratin, type I cytoskeletal 28 [KO:K07604]
114706941  keratin, type I cuticular Ha1 [KO:K07604]
114706942  keratin, type I cuticular Ha6 [KO:K07604]
114706945  Krt13; keratin, type I cytoskeletal 13 [KO:K07604]
114706948  Krt34; keratin, type I cuticular Ha4 [KO:K07604]
114706949  LOW QUALITY PROTEIN: keratin, type I cuticular Ha3-I-like [KO:K07604]
114706950  Krt23; keratin, type I cytoskeletal 23 [KO:K07604]
114706951  LOW QUALITY PROTEIN: keratin, type I cuticular Ha3-II-like [KO:K07604]
114706953  Krt12; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 12 [KO:K07604]
114706955  Krt27; keratin, type I cytoskeletal 27 [KO:K07604]
114706958  Krt40; keratin, type I cytoskeletal 40 [KO:K07604]
114706970  Krt26; keratin, type I cytoskeletal 26 [KO:K07604]
114706971  Krt39; keratin, type I cytoskeletal 39 [KO:K07604]
114706977  Krt9; keratin, type I cytoskeletal 9 [KO:K07604]
114706978  keratin, type I cytoskeletal 14 [KO:K07604]
114706979  Krt19; keratin, type I cytoskeletal 19 [KO:K07604]
114707007  Krt10; keratin, type I cytoskeletal 10 isoform X2 [KO:K07604]
114696565  Krt18; keratin, type I cytoskeletal 18 [KO:K07604]
114694043  Ctsd; cathepsin D [KO:K01379] [EC:3.4.23.5]
114698835  Greb1; LOW QUALITY PROTEIN: protein GREB1 [KO:K27477]
114703969  Tff1; trefoil factor 1 [KO:K22456]
114695676  Pgr; progesterone receptor [KO:K08556]
114680857  Tgfa; protransforming growth factor alpha isoform X1 [KO:K08774]
114706921  Rara; retinoic acid receptor alpha isoform X1 [KO:K08527]
114698038  Fos; proto-oncogene c-Fos [KO:K04379]
114693768  Jun; transcription factor AP-1 [KO:K04448]
114696625  Sp1; transcription factor Sp1 isoform X1 [KO:K04684]
114682203  Gper1; G-protein coupled estrogen receptor 1 [KO:K04246]
114682025  neuroendocrine secretory protein 55-like [KO:K04632]
114682029  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
114681835  Src; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
114694533  Mmp2; LOW QUALITY PROTEIN: 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
114692635  Mmp9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
114705134  Hbegf; proheparin-binding EGF-like growth factor [KO:K08523]
114693962  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
114696121  Adcy2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
114697107  Adcy3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
114708701  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
114704841  Adcy5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
114708522  Adcy6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
114708501  Adcy7; LOW QUALITY PROTEIN: adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
114697724  Adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
114710615  Adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
114684152  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
114698264  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
114705057  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
114700827  Atf2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
114687991  LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
114694285  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
114691010  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
114688126  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
114699702  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
114707907  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
114703207  Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
114689726  Creb5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
114705847  Atf6b; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
114705532  Egfr; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
114707889  Shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
114684102  Shc2; SHC-transforming protein 2 [KO:K17447]
114689488  Shc3; SHC-transforming protein 3 [KO:K17448]
114683897  Shc4; LOW QUALITY PROTEIN: SHC-transforming protein 4 [KO:K17449]
114707024  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
114684224  Sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
114681621  Sos1; son of sevenless homolog 1 [KO:K03099]
114685127  GTPase HRas-like [KO:K02833]
114688488  GTPase HRas-like [KO:K02833]
114693493  GTPase HRas-like [KO:K02833]
114693595  Hras; GTPase HRas isoform X1 [KO:K02833]
114696553  GTPase HRas-like [KO:K02833]
114708477  Kras; GTPase KRas isoform X2 [KO:K07827]
114698582  Nras; GTPase NRas [KO:K07828]
114689636  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
114691497  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
114688121  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
114682732  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
114704332  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
114710523  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
114684032  Pik3cd; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
114693559  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
114695335  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
114688966  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
114706924  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
114703850  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
114690660  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
114681524  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
114703046  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
114682700  Gabbr1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
114702349  Gabbr2; LOW QUALITY PROTEIN: gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
114710969  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
114699988  Gnai3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
114708228  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
114694517  Gnao1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
114696693  Kcnj3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
114700364  Kcnj6; G protein-activated inward rectifier potassium channel 2 isoform X1 [KO:K05000]
114690693  Kcnj9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
114699783  Kcnj5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
114697442  Pomc; pro-opiomelanocortin [KO:K05228]
114680886  Oprm1; mu-type opioid receptor [KO:K04215]
114708186  Prkcd; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
114696911  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
114680674  Plcb3; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
114705921  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
114703666  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X2 [KO:K05858] [EC:3.1.4.11]
114703672  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
114691978  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
114708393  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
114706123  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
114691640  Calml4; calmodulin-like protein 4 isoform X2 [KO:K02183]
114681418  Calm3; calmodulin-3 [KO:K02183]
114705020  Calm1; calmodulin-1 [KO:K02183]
114708260  Calml6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
114708768  calmodulin-4-like [KO:K02183]
114708779  Calml3; calmodulin-like protein 3 [KO:K02183]
114709209  Calm2; calmodulin-2 [KO:K02183]
114700088  Nos3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
114686464  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
pleu04010  MAPK signaling pathway
pleu04020  Calcium signaling pathway
pleu04151  PI3K-Akt signaling pathway
pleu04270  Vascular smooth muscle contraction
pleu04727  GABAergic synapse
pleu04913  Ovarian steroidogenesis
KO pathway
ko04915   
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