KEGG   PATHWAY: mun04915
Entry
mun04915                    Pathway                                
Name
Estrogen signaling pathway - Meriones unguiculatus (Mongolian gerbil)
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
mun04915  Estrogen signaling pathway
mun04915

Other DBs
GO: 0030520
Organism
Meriones unguiculatus (Mongolian gerbil) [GN:mun]
Gene
110566125  Esr1; estrogen receptor [KO:K08550]
110547771  Esr2; estrogen receptor beta isoform X2 [KO:K08551]
110555839  Hsp90ab1; heat shock protein HSP 90-beta [KO:K04079]
110553235  Hsp90aa1; heat shock protein HSP 90-alpha [KO:K04079]
110563924  Hsp90b1; endoplasmin [KO:K09487]
110544024  Fkbp5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
110563598  Fkbp4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
110560143  Hspa1l; heat shock 70 kDa protein 1-like [KO:K03283]
110560130  heat shock 70 kDa protein 1A [KO:K03283]
110552032  Hspa8; heat shock cognate 71 kDa protein [KO:K03283]
110554439  Hspa6; LOW QUALITY PROTEIN: heat shock 70 kDa protein 6 [KO:K03283]
110555190  Ncoa1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
110559511  Ncoa2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
110549109  Ncoa3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
110557800  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
110566084  Ebag9; receptor-binding cancer antigen expressed on SiSo cells isoform X5 [KO:K22455]
110541625  Krt9; keratin, type I cytoskeletal 9 [KO:K07604]
110544098  keratin, type I cytoskeletal 16-like [KO:K07604]
110544388  keratin, type I cuticular Ha1 [KO:K07604]
110542375  keratin, type I cuticular Ha3-II-like [KO:K07604]
110542376  keratin, type I cuticular Ha3-I [KO:K07604]
110542387  keratin, type I cytoskeletal 28 [KO:K07604]
110542388  Krt10; keratin, type I cytoskeletal 10 isoform X1 [KO:K07604]
110539359  Krt24; keratin, type I cytoskeletal 24 isoform X1 [KO:K07604]
110539361  keratin, type I cytoskeletal 27 [KO:K07604]
110539364  keratin, type I cytoskeletal 26 [KO:K07604]
110539365  keratin, type I cytoskeletal 25 [KO:K07604]
110539407  Krt32; keratin, type I cuticular Ha2 [KO:K07604]
110539408  Krt35; keratin, type I cuticular Ha5 [KO:K07604]
110539409  keratin, type I cuticular Ha6 [KO:K07604]
110539410  Krt13; keratin, type I cytoskeletal 13 [KO:K07604]
110539411  LOW QUALITY PROTEIN: keratin, type I cuticular Ha4-like [KO:K07604]
110539412  Krt15; keratin, type I cytoskeletal 15 [KO:K07604]
110539413  Krt19; keratin, type I cytoskeletal 19 [KO:K07604]
110541626  keratin, type I cytoskeletal 14 [KO:K07604]
110552324  Krt18; keratin, type I cytoskeletal 18 [KO:K07604]
110564616  Krt23; keratin, type I cytoskeletal 23 [KO:K07604]
110564617  Krt12; keratin, type I cytoskeletal 12 [KO:K07604]
110564618  Krt40; keratin, type I cytoskeletal 40 isoform X1 [KO:K07604]
110564624  Krt20; keratin, type I cytoskeletal 20 isoform X1 [KO:K07604]
110563579  keratin, type I cytoskeletal 17 isoform X1 [KO:K07604]
110563581  keratin, type I cytoskeletal 16 [KO:K07604]
110563582  keratin, type I cytoskeletal 42 [KO:K07604]
110541624  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 16-like [KO:K07604]
110564615  Krt39; keratin, type I cytoskeletal 39 [KO:K07604]
110546566  Ctsd; cathepsin D [KO:K01379] [EC:3.4.23.5]
110541577  Greb1; protein GREB1 isoform X2 [KO:K27477]
110553304  Tff1; trefoil factor 1 [KO:K22456]
110552199  Pgr; progesterone receptor [KO:K08556]
110547163  Tgfa; protransforming growth factor alpha [KO:K08774]
110558507  Rara; retinoic acid receptor alpha isoform X1 [KO:K08527]
110546962  Fos; protein c-Fos [KO:K04379]
110559727  Jun; transcription factor Jun [KO:K04448]
110552322  Sp1; transcription factor Sp1 isoform X1 [KO:K04684]
110550693  Gper1; G-protein coupled estrogen receptor 1 [KO:K04246]
110563608  neuroendocrine secretory protein 55-like [KO:K04632]
110566227  Src; proto-oncogene tyrosine-protein kinase Src isoform X2 [KO:K05704] [EC:2.7.10.2]
110545189  Mmp2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
110549307  Mmp9; matrix metalloproteinase-9 isoform X1 [KO:K01403] [EC:3.4.24.35]
110557378  Hbegf; proheparin-binding EGF-like growth factor [KO:K08523]
110555169  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
110550962  Adcy2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
110555185  Adcy3; adenylate cyclase type 3 isoform X3 [KO:K08043] [EC:4.6.1.1]
110556521  Adcy4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
110547229  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
110559444  Adcy6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
110560723  Adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
110561696  Adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
110545944  Adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
110545842  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
110555016  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
110551437  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
110556579  Atf2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
110564629  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
110549859  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
110555614  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
110549233  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
110554250  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
110561882  Creb3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
110554970  Creb5; cyclic AMP-responsive element-binding protein 5 isoform X2 [KO:K09047]
110565383  Atf6b; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
110539539  Egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
110551574  Shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
110551355  Shc2; SHC-transforming protein 2 isoform X4 [KO:K17447]
110559069  Shc3; SHC-transforming protein 3 [KO:K17448]
110550937  Shc4; SHC-transforming protein 4 [KO:K17449]
110547825  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
110547073  Sos1; son of sevenless homolog 1 isoform X1 [KO:K03099]
110556913  Sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
110553931  Hras; GTPase HRas isoform X1 [KO:K02833]
110558913  Kras; GTPase KRas isoform X1 [KO:K07827]
110544642  GTPase NRas [KO:K07828]
110544765  Nras; GTPase NRas [KO:K07828]
110550814  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
110559000  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110555605  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
110553796  Mapk1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
110547978  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
110565112  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110556252  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
110548394  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110553683  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110549145  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
110563512  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
110556719  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110558966  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110564898  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110551130  Gabbr2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
110563047  Gabbr1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
110539607  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
110545517  Gnai3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
110564775  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
110561150  Gnao1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
110540987  Kcnj3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
110566853  Kcnj6; G protein-activated inward rectifier potassium channel 2 isoform X1 [KO:K05000]
110556712  Kcnj9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
110543240  Kcnj5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
110555189  Pomc; pro-opiomelanocortin [KO:K05228]
110565466  Oprm1; mu-type opioid receptor isoform X1 [KO:K04215]
110547587  Prkcd; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
110562511  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
110563159  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
110555720  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
110551595  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
110550598  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
110552142  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
110558908  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
110543748  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
110561484  Calm1; calmodulin-1 [KO:K02183]
110562918  Calm2; calmodulin-2 [KO:K02183]
110552646  Calm3; calmodulin-3 [KO:K02183]
110550527  Calml4; calmodulin-like protein 4 isoform X1 [KO:K02183]
110560701  Calml3; calmodulin-like protein 3 [KO:K02183]
110560702  calmodulin-4-like [KO:K02183]
110562552  Nos3; nitric oxide synthase 3 isoform X1 [KO:K13242] [EC:1.14.13.39]
110566206  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
mun04010  MAPK signaling pathway
mun04020  Calcium signaling pathway
mun04151  PI3K-Akt signaling pathway
mun04270  Vascular smooth muscle contraction
mun04727  GABAergic synapse
mun04913  Ovarian steroidogenesis
KO pathway
ko04915   
LinkDB

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