KEGG   PATHWAY: hgl04915
Entry
hgl04915                    Pathway                                
Name
Estrogen signaling pathway - Heterocephalus glaber (naked mole-rat)
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
hgl04915  Estrogen signaling pathway
hgl04915

Other DBs
GO: 0030520
Organism
Heterocephalus glaber (naked mole-rat) [GN:hgl]
Gene
101715977  Esr1; estrogen receptor 1 [KO:K08550]
101708704  Esr2; estrogen receptor 2 [KO:K08551]
101725326  Hsp90aa1; heat shock protein 90 alpha family class A member 1 [KO:K04079]
101710837  heat shock protein HSP 90-alpha-like [KO:K04079]
101726120  heat shock protein HSP 90-beta-like [KO:K04079]
101699803  Hsp90ab1; heat shock protein 90 alpha family class B member 1 [KO:K04079]
101704175  Hsp90b1; heat shock protein 90 beta family member 1 [KO:K09487]
101718430  Fkbp5; FK506 binding protein 5 [KO:K09571] [EC:5.2.1.8]
101711168  Fkbp4; FK506 binding protein 4 [KO:K09571] [EC:5.2.1.8]
101699805  Hspa1l; heat shock 70 kDa protein 1-like [KO:K03283]
101700637  heat shock 70 kDa protein 1B [KO:K03283]
101701238  Hspa6; heat shock protein family A (Hsp70) member 6 [KO:K03283]
101708313  Hspa8; heat shock protein family A (Hsp70) member 8 [KO:K03283]
101726578  Ncoa1; nuclear receptor coactivator 1 [KO:K09101] [EC:2.3.1.48]
101700727  Ncoa2; nuclear receptor coactivator 2 [KO:K11255]
101708253  Ncoa3; nuclear receptor coactivator 3 [KO:K11256] [EC:2.3.1.48]
101701667  Bcl2; BCL2, apoptosis regulator [KO:K02161]
101725035  Ebag9; estrogen receptor binding site associated, antigen, 9 [KO:K22455]
101715002  Krt18; keratin 18 [KO:K07604]
101717715  Krt26; keratin 26 [KO:K07604]
101726336  Krt32; keratin, type I cuticular Ha1 [KO:K07604]
101696566  Krt33b; keratin, type I cuticular Ha3-II [KO:K07604]
101700966  Krt40; keratin 40 [KO:K07604]
101701320  Krt39; keratin 39 [KO:K07604]
101709675  Krt35; keratin 35 [KO:K07604]
101708719  Krt13; keratin 13 [KO:K07604]
101706925  Krt17; keratin, type I cytoskeletal 17 [KO:K07604]
101707650  Krt14; keratin, type I cytoskeletal 14 [KO:K07604]
101709325  Krt36; keratin 36 [KO:K07604]
101716435  Krt10; keratin 10 [KO:K07604]
101707284  Krt16; keratin, type I cytoskeletal 16 [KO:K07604]
101718617  Krt24; keratin 24 [KO:K07604]
101710019  Krt33a; keratin 33A [KO:K07604]
101717378  Krt27; keratin, type I cytoskeletal 27 [KO:K07604]
101715514  Krt23; keratin 23 [KO:K07604]
101718265  Krt25; keratin 25 [KO:K07604]
101717028  Krt28; keratin 28 [KO:K07604]
101716094  Krt12; keratin 12 [KO:K07604]
101708366  Krt15; keratin 15 [KO:K07604]
101708019  Krt19; keratin 19 [KO:K07604]
101706553  keratin, type I cytoskeletal 42-like [KO:K07604]
101716979  Ctsd; cathepsin D [KO:K01379] [EC:3.4.23.5]
101706488  Greb1; growth regulation by estrogen in breast cancer 1 [KO:K27477]
101723243  Pgr; progesterone receptor [KO:K08556]
101723712  Tgfa; transforming growth factor alpha [KO:K08774]
101722948  Rara; retinoic acid receptor alpha [KO:K08527]
101718383  Fos; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
101722197  Jun; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
101697506  Sp1; Sp1 transcription factor [KO:K04684]
101702826  Gper1; G protein-coupled estrogen receptor 1 [KO:K04246]
101716905  Gnas; GNAS complex locus [KO:K04632]
101705689  guanine nucleotide-binding protein G(s) subunit alpha isoforms short [KO:K04632]
101703827  Src; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
101696977  Mmp2; matrix metallopeptidase 2 [KO:K01398] [EC:3.4.24.24]
101717243  Mmp9; matrix metallopeptidase 9 [KO:K01403] [EC:3.4.24.35]
101699647  Hbegf; heparin binding EGF like growth factor [KO:K08523]
101711366  Adcy1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
101718304  Adcy2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
101713887  Adcy3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
101719464  Adcy4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
101702436  Adcy5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
101698189  Adcy6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
101712483  Adcy7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
101698293  Adcy8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
101714605  Adcy9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
101707235  Prkaca; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
101721558  Prkacb; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
101712503  Creb1; cAMP responsive element binding protein 1 [KO:K05870]
101717365  Atf2; activating transcription factor 2 [KO:K04450]
101724287  Atf4; activating transcription factor 4 [KO:K04374]
101715715  Creb3l2; cAMP responsive element binding protein 3 like 2 [KO:K09048]
101698748  Creb3l1; cAMP responsive element binding protein 3 like 1 [KO:K09048]
101716023  Creb3l3; cAMP responsive element binding protein 3 like 3 [KO:K09048]
101706643  Creb3l4; cAMP responsive element binding protein 3 like 4 [KO:K09048]
101718447  Creb3; cAMP responsive element binding protein 3 [KO:K09048]
101703315  Creb5; cAMP responsive element binding protein 5 [KO:K09047]
101715793  Atf6b; activating transcription factor 6 beta [KO:K09049]
101723771  Egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
101717434  Shc1; SHC adaptor protein 1 [KO:K06279]
101723930  Shc2; SHC adaptor protein 2 [KO:K17447]
101715363  Shc3; SHC adaptor protein 3 [KO:K17448]
101717788  Shc4; SHC adaptor protein 4 [KO:K17449]
101717035  Grb2; growth factor receptor bound protein 2 [KO:K04364]
101707893  Sos1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
101701753  Sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
101716053  Hras; HRas proto-oncogene, GTPase [KO:K02833]
101718997  Kras; KRAS proto-oncogene, GTPase [KO:K07827]
101719269  Nras; neuroblastoma RAS viral oncogene homolog [KO:K07828]
101721841  Raf1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
101715628  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101707562  Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101706099  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101702687  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101711934  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
101715249  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
101712941  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
101718815  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
101717096  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
101703691  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
101700695  Akt1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
101719164  Akt2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
101701289  Akt3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
101719480  Gabbr1; gamma-aminobutyric acid type B receptor subunit 1 [KO:K04615]
101719923  Gabbr2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
101698645  Gnai2; G protein subunit alpha i2 [KO:K04630]
101702965  Gnai1; G protein subunit alpha i1 [KO:K04630]
101703043  Gnai3; G protein subunit alpha i3 [KO:K04630]
101723580  Gnao1; G protein subunit alpha o1 [KO:K04534]
101718832  Kcnj3; potassium voltage-gated channel subfamily J member 3 [KO:K04997]
101719327  Kcnj6; potassium voltage-gated channel subfamily J member 6 [KO:K05000]
101722613  Kcnj9; potassium voltage-gated channel subfamily J member 9 [KO:K05002]
101720856  Kcnj5; potassium voltage-gated channel subfamily J member 5 [KO:K04999]
101718053  Pomc; proopiomelanocortin [KO:K05228]
100897068  Oprm1; opioid receptor mu 1 [KO:K04215]
101718422  Prkcd; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
101715420  Gnaq; G protein subunit alpha q [KO:K04634]
101725860  Plcb1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
101696454  Plcb4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
101697744  Plcb3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
101708380  Plcb2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
101706047  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
101716022  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101706978  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101704751  Calm2; calmodulin 2 [KO:K02183]
101713746  Calm1; calmodulin 1 [KO:K02183]
101724181  Calm3; calmodulin 3 [KO:K02183]
101716865  Calml3; calmodulin like 3 [KO:K02183]
101725309  Calml5; calmodulin like 5 [KO:K02183]
101714220  calmodulin-like [KO:K02183]
101712577  Calml6; calmodulin like 6 [KO:K02183]
101707626  Calml4; calmodulin like 4 [KO:K02183]
101711110  Nos3; nitric oxide synthase 3 [KO:K13242] [EC:1.14.13.39]
101712477  Grm1; glutamate metabotropic 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
hgl04010  MAPK signaling pathway
hgl04020  Calcium signaling pathway
hgl04151  PI3K-Akt signaling pathway
hgl04270  Vascular smooth muscle contraction
hgl04727  GABAergic synapse
hgl04913  Ovarian steroidogenesis
KO pathway
ko04915   
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