KEGG   PATHWAY: cfa04915
Entry
cfa04915                    Pathway                                
Name
Estrogen signaling pathway - Canis lupus familiaris (dog)
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
cfa04915  Estrogen signaling pathway
cfa04915

Other DBs
GO: 0030520
Organism
Canis lupus familiaris (dog) [GN:cfa]
Gene
403640  ESR1; estrogen receptor [KO:K08550]
403639  ESR2; estrogen receptor beta [KO:K08551]
480438  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
474919  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
100687242  LOW QUALITY PROTEIN: heat shock protein HSP 90-beta-like [KO:K04079]
404019  HSP90B1; endoplasmin precursor [KO:K09487]
477726  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 isoform X2 [KO:K09571] [EC:5.2.1.8]
481759  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 isoform X5 [KO:K09571] [EC:5.2.1.8]
474850  heat shock 70 kDa protein 1-like isoform X1 [KO:K03283]
403612  HSP70; heat shock 70 kDa protein 1 [KO:K03283]
479406  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
119873859  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like isoform X2 [KO:K03283]
607182  heat shock cognate 71 kDa protein-like [KO:K03283]
475684  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
486989  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
119865679  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
403416  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
403500  EBAG9; receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
490977  KRT17; keratin, type I cytoskeletal 17 [KO:K07604]
490984  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
490985  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
490986  KRT38; keratin, type I cuticular Ha8 [KO:K07604]
490987  KRT37; keratin, type I cuticular Ha8 [KO:K07604]
490988  KRT31; keratin, type I cuticular Ha1 [KO:K07604]
490989  KRT34; keratin, type I cuticular Ha4 [KO:K07604]
490991  KRT33A; keratin, type I cuticular Ha3-I [KO:K07604]
491004  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
607814  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
607848  KRT41; keratin, type I cuticular Ha7 [KO:K07604]
490980  KRT9; keratin, type I cytoskeletal 9 [KO:K07604]
608072  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
477601  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
491006  KRT10; keratin, type I cytoskeletal 10 isoform X1 [KO:K07604]
490978  KRT16; keratin, type I cytoskeletal 16 [KO:K07604]
491005  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
100034663  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
490976  KRT42; keratin, type I cytoskeletal 42 isoform X1 [KO:K07604]
490983  KRT13; keratin, type I cytoskeletal 13 [KO:K07604]
491007  KRT27; keratin, type I cytoskeletal 27 [KO:K07604]
491009  KRT24; keratin, type I cytoskeletal 24 [KO:K07604]
607876  KRT33B; keratin 33B [KO:K07604]
608094  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
608107  KRT28; keratin, type I cytoskeletal 28 [KO:K07604]
100685481  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
100685323  KRT14; keratin 14 [KO:K07604]
100685404  KRT15; keratin, type I cytoskeletal 15 [KO:K07604]
100686957  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
491008  KRT26; keratin, type I cytoskeletal 26 [KO:K07604]
483662  CTSD; cathepsin D precursor [KO:K01379] [EC:3.4.23.5]
610007  GREB1; protein GREB1 isoform X1 [KO:K27477]
403491  TFF1; trefoil factor 1 precursor [KO:K22456]
403621  PGR; progesterone receptor [KO:K08556]
403431  TGFA; protransforming growth factor alpha [KO:K08774]
480526  RARA; retinoic acid receptor alpha [KO:K08527]
490792  FOS; proto-oncogene c-Fos [KO:K04379]
609429  JUN; transcription factor AP-1 [KO:K04448]
486507  SP1; transcription factor Sp1 isoform X2 [KO:K04684]
480808  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
403943  GNAS; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
485864  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
403733  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
403885  MMP9; matrix metalloproteinase-9 precursor [KO:K01403] [EC:3.4.24.35]
607007  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
607357  ADCY1; LOW QUALITY PROTEIN: adenylate cyclase type 1 isoform X5 [KO:K08041] [EC:4.6.1.1]
478624  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
482994  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
480271  ADCY4; adenylate cyclase type 4 isoform X2 [KO:K08044] [EC:4.6.1.1]
403859  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
477625  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
487289  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
482045  ADCY8; adenylate cyclase type 8 isoform X2 [KO:K08048] [EC:4.6.1.1]
490031  ADCY9; adenylate cyclase type 9 isoform X2 [KO:K08049] [EC:4.6.1.1]
403556  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
479975  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X2 [KO:K04345] [EC:2.7.11.11]
607922  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
478806  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
474503  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
611934  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X2 [KO:K09048]
483636  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
491369  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
485046  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
612303  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
475266  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X5 [KO:K09047]
474855  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
404306  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
490439  SHC1; SHC-transforming protein 1 [KO:K06279]
611955  SHC2; SHC-transforming protein 2 isoform X2 [KO:K17447]
476352  SHC3; SHC-transforming protein 3 [KO:K17448]
487546  SHC4; SHC-transforming protein 4 isoform X2 [KO:K17449]
483312  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
490682  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
403735  HRAS; GTPase HRas isoform 1 [KO:K02833]
403871  KRAS; GTPase KRas isoform X1 [KO:K07827]
403872  NRAS; GTPase NRas [KO:K07828]
484648  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
478347  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
611939  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
477575  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100855877  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
488084  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
489644  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X3 [KO:K00922] [EC:2.7.1.153]
477085  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
609956  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
487235  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100856339  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
442964  AKT3; RAC-gamma serine/threonine-protein kinase isoform X8 [KO:K04456] [EC:2.7.11.1]
449021  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
490878  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
488340  GABBR1; LOW QUALITY PROTEIN: gamma-aminobutyric acid type B receptor subunit 1 isoform X4 [KO:K04615]
481627  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 isoform X1 [KO:K04615]
442957  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
478227  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
611810  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha isoform X2 [KO:K04630]
609157  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
488355  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X3 [KO:K04997]
487756  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
100855823  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
489284  KCNJ5; G protein-activated inward rectifier potassium channel 4 isoform X5 [KO:K04999]
403659  POMC; pro-opiomelanocortin [KO:K05228]
484041  OPRM1; mu-type opioid receptor [KO:K04215]
494005  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
403928  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
477160  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
485773  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
476034  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X2 [KO:K05858] [EC:3.1.4.11]
100856190  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
476548  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
486628  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X2 [KO:K04959]
481746  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
474584  CALM2; calmodulin-2 [KO:K02183]
607269  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
487146  CALML5; calmodulin-like protein 5 [KO:K02183]
480416  CALM1; calmodulin-1 [KO:K02183]
476428  CALM3; calmodulin-3 isoform X2 [KO:K02183]
478351  CALML4; calmodulin-like protein 4 isoform X2 [KO:K02183]
102153034  calmodulin-like protein 3 [KO:K02183]
403784  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
484024  GRM1; metabotropic glutamate receptor 1 isoform X2 [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
cfa04010  MAPK signaling pathway
cfa04020  Calcium signaling pathway
cfa04151  PI3K-Akt signaling pathway
cfa04270  Vascular smooth muscle contraction
cfa04727  GABAergic synapse
cfa04913  Ovarian steroidogenesis
KO pathway
ko04915   
LinkDB

DBGET integrated database retrieval system