KEGG   PATHWAY: lcat04915
Entry
lcat04915                   Pathway                                
Name
Estrogen signaling pathway - Lemur catta (Ring-tailed lemur)
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
lcat04915  Estrogen signaling pathway
lcat04915

Other DBs
GO: 0030520
Organism
Lemur catta (Ring-tailed lemur) [GN:lcat]
Gene
123633382  ESR1; estrogen receptor isoform X1 [KO:K08550]
123648194  ESR2; estrogen receptor beta isoform X1 [KO:K08551]
123622409  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
123631934  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
123639365  HSP90B1; endoplasmin [KO:K09487]
123632857  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
123640166  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
123631751  heat shock 70 kDa protein 1-like isoform X1 [KO:K03283]
123631752  heat shock 70 kDa protein 1-like [KO:K03283]
123631753  heat shock 70 kDa protein 1 [KO:K03283]
123647169  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
123641226  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
123648561  heat shock cognate 71 kDa protein [KO:K03283]
123636668  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
123645013  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
123622298  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
123621883  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
123644624  EBAG9; receptor-binding cancer antigen expressed on SiSo cells isoform X1 [KO:K22455]
123620922  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
123620923  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
123620924  KRT9; keratin, type I cytoskeletal 9 [KO:K07604]
123620925  KRT14; keratin, type I cytoskeletal 14 [KO:K07604]
123620926  KRT16; keratin, type I cytoskeletal 16 [KO:K07604]
123620927  KRT15; keratin, type I cytoskeletal 15 [KO:K07604]
123620928  KRT13; keratin, type I cytoskeletal 13 [KO:K07604]
123620929  KRT17; keratin, type I cytoskeletal 17 [KO:K07604]
123620930  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
123621179  KRT26; keratin, type I cytoskeletal 26 [KO:K07604]
123621186  keratin, type I cuticular Ha7-like [KO:K07604]
123621187  keratin, type I cuticular Ha7-like [KO:K07604]
123621188  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 42-like [KO:K07604]
123628703  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 18-like [KO:K07604]
123644600  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 18-like [KO:K07604]
123639787  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
123639953  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 18-like [KO:K07604]
123640676  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 18-like [KO:K07604]
123625736  keratin, type I cytoskeletal 18-like [KO:K07604]
123620874  keratin, type I cytoskeletal 24-like [KO:K07604]
123620875  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
123620880  keratin, type I cytoskeletal 24-like [KO:K07604]
123620882  KRT27; keratin, type I cytoskeletal 27 [KO:K07604]
123620883  KRT28; keratin, type I cytoskeletal 28 [KO:K07604]
123620884  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
123620885  KRT10; keratin, type I cytoskeletal 10 [KO:K07604]
123620887  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
123620888  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
123620889  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
123620890  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
123620915  keratin, type I cuticular Ha3-I-like isoform X1 [KO:K07604]
123620916  keratin, type I cuticular Ha3-I [KO:K07604]
123620918  LOW QUALITY PROTEIN: keratin, type I cuticular Ha4-like [KO:K07604]
123620919  keratin, type I cuticular Ha1 [KO:K07604]
123620920  keratin, type I cuticular Ha8-like [KO:K07604]
123620921  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
123642904  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
123636601  GREB1; protein GREB1 [KO:K27477]
123641934  PGR; progesterone receptor isoform X1 [KO:K08556]
123637024  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
123620865  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
123646534  FOS; proto-oncogene c-Fos [KO:K04379]
123635592  JUN; transcription factor AP-1 [KO:K04448]
123639764  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
123632546  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
123622308  neuroendocrine secretory protein 55-like [KO:K04632]
123622310  guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632]
123622361  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
123625360  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
123622569  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
123637855  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
123647256  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
123648063  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
123636670  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
123650680  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
123630472  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
123640442  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
123625466  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
123644339  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
123632319  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
123637748  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
123635476  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
123644073  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
123643408  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
123640339  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
123646158  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
123647675  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
123633885  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
123634008  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
123642645  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
123647634  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
123631772  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
123647442  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
123634038  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
123632067  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
123645857  SHC3; SHC-transforming protein 3 [KO:K17448]
123622389  SHC4; SHC-transforming protein 4 [KO:K17449]
123650792  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
123636823  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
123649468  SOS2; son of sevenless homolog 2 [KO:K03099]
123642937  HRAS; GTPase HRas isoform X1 [KO:K02833]
123639921  KRAS; GTPase KRas [KO:K07827]
123635081  NRAS; GTPase NRas [KO:K07828]
123638125  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
123631625  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
123633879  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
123632778  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
123626228  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
123629856  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123630278  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
123634506  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
123639706  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
123648578  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
123634187  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
123624322  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
123627566  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
123643797  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123646636  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
123632808  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
123623249  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
123647150  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
123635002  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
123625313  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
123650029  G protein-activated inward rectifier potassium channel 1-like [KO:K04997]
123643345  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
123630738  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
123635181  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
123640996  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
123636675  POMC; pro-opiomelanocortin [KO:K05228]
123633394  OPRM1; mu-type opioid receptor isoform X1 [KO:K04215]
123623170  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
123646308  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
123622057  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
123622065  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
123624366  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
123641430  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
123623574  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
123639915  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
123632820  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
123636893  CALM2; calmodulin-2 [KO:K02183]
123645611  CALM1; calmodulin-1 [KO:K02183]
123623035  CALML3; calmodulin-like protein 3 [KO:K02183]
123623036  CALML5; calmodulin-like protein 5 [KO:K02183]
123631755  CALML4; calmodulin-like protein 4 [KO:K02183]
123623919  CALM3; calmodulin-3 [KO:K02183]
123634905  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
123636681  calmodulin-alpha-like [KO:K02183]
123647518  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
123633346  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
lcat04010  MAPK signaling pathway
lcat04020  Calcium signaling pathway
lcat04151  PI3K-Akt signaling pathway
lcat04270  Vascular smooth muscle contraction
lcat04727  GABAergic synapse
lcat04913  Ovarian steroidogenesis
KO pathway
ko04915   
LinkDB

DBGET integrated database retrieval system