KEGG   PATHWAY: aml04915
Entry
aml04915                    Pathway                                
Name
Estrogen signaling pathway - Ailuropoda melanoleuca (giant panda)
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
aml04915  Estrogen signaling pathway
aml04915

Other DBs
GO: 0030520
Organism
Ailuropoda melanoleuca (giant panda) [GN:aml]
Gene
100463678  RARA; retinoic acid receptor alpha isoform X3 [KO:K08527]
100463775  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100463921  [KO:K07604]
100464170  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
100464196  NRAS; GTPase NRas [KO:K07828]
100464423  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
100464463  EBAG9; receptor-binding cancer antigen expressed on SiSo cells isoform X2 [KO:K22455]
100464669  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
100464853  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
100464919  KRT15; keratin, type I cytoskeletal 15 isoform X2 [KO:K07604]
100464994  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
100465166  [KO:K07604]
100465178  KRT24; keratin, type I cytoskeletal 24 [KO:K07604]
100465232  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
100465417  KRT17; keratin, type I cytoskeletal 17 [KO:K07604]
100465430  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
100465448  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
100465459  OPRM1; mu-type opioid receptor isoform X1 [KO:K04215]
100465682  KRT27; keratin, type I cytoskeletal 27 [KO:K07604]
100465700  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100465793  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100465932  [KO:K07604]
100465973  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
100466101  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
100466130  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X2 [KO:K04534]
100466175  GREB1; protein GREB1 isoform X6 [KO:K27477]
100466183  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
100466408  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
100466427  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
100466965  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
100467161  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X8 [KO:K04958]
100467363  HSP90AA1; LOW QUALITY PROTEIN: heat shock protein HSP 90-alpha [KO:K04079]
100467713  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
100467724  TGFA; protransforming growth factor alpha isoform X3 [KO:K08774]
100467916  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100468080  SHC3; SHC-transforming protein 3 [KO:K17448]
100468159  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
100468252  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X2 [KO:K04345] [EC:2.7.11.11]
100468579  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
100468647  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
100468763  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100468801  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
100468916  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
100469231  [KO:K04632]
100469467  HSPA6; LOW QUALITY PROTEIN: heat shock 70 kDa protein 6 [KO:K03283]
100469628  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
100470035  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100470377  KRT26; keratin, type I cytoskeletal 26 [KO:K07604]
100470629  KRT10; keratin, type I cytoskeletal 10 isoform X1 [KO:K07604]
100470867  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
100470884  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
100470909  CALM2; calmodulin-2 [KO:K02183]
100471134  KRT23; keratin, type I cytoskeletal 23 isoform X1 [KO:K07604]
100471164  ADCY3; adenylate cyclase type 3 isoform X2 [KO:K08043] [EC:4.6.1.1]
100471384  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
100471414  HSP90AB1; LOW QUALITY PROTEIN: heat shock protein HSP 90-beta [KO:K04079]
100471498  ESR2; estrogen receptor beta [KO:K08551]
100471747  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
100471767  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
100471908  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
100471940  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
100472104  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
100472122  CALM3; calmodulin-3 [KO:K02183]
100472388  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100472621  TFF1; trefoil factor 1 [KO:K22456]
100472777  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100473195  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
100473291  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
100473680  [KO:K04632]
100473836  HRAS; GTPase HRas isoform X1 [KO:K02833]
100474020  HSP90B1; endoplasmin [KO:K09487]
100474121  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
100474135  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X2 [KO:K04450]
100474261  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
100474271  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
100474396  SOS2; son of sevenless homolog 2 isoform X9 [KO:K03099]
100474779  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
100474867  FOS; proto-oncogene c-Fos [KO:K04379]
100474980  [KO:K07604]
100474983  SP1; transcription factor Sp1 [KO:K04684]
100475137  SHC4; SHC-transforming protein 4 isoform X2 [KO:K17449]
100475237  [KO:K07604]
100475291  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100475429  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
100475729  [KO:K07604]
100475976  [KO:K07604]
100476017  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X2 [KO:K09049]
100476183  MMP2; 72 kDa type IV collagenase isoform X1 [KO:K01398] [EC:3.4.24.24]
100476284  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100476478  KRT13; keratin, type I cytoskeletal 13 [KO:K07604]
100476495  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
100476699  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
100476730  KRT9; keratin, type I cytoskeletal 9 [KO:K07604]
100476786  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
100476922  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
100476975  KRT16; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 16 [KO:K07604]
100477226  [KO:K07604]
100477711  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
100477888  ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100478039  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100478600  CALML6; calmodulin-like protein 6 [KO:K02183]
100478732  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
100479294  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100479526  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
100479580  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
100479929  GRM1; metabotropic glutamate receptor 1 isoform X1 [KO:K04603]
100480134  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
100480290  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
100480414  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100480603  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
100480694  SHC2; LOW QUALITY PROTEIN: SHC-transforming protein 2 [KO:K17447]
100480856  SHC1; SHC-transforming protein 1 isoform X2 [KO:K06279]
100481177  CALM1; calmodulin-1 [KO:K02183]
100481387  PGR; progesterone receptor [KO:K08556]
100481656  POMC; LOW QUALITY PROTEIN: pro-opiomelanocortin [KO:K05228]
100481755  PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
100481918  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
100482255  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100482382  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
100482519  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
100482526  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
100483310  [KO:K03283]
100483482  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
100483558  [KO:K03283]
100483828  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100483834  JUN; transcription factor AP-1 [KO:K04448]
100483919  KRAS; GTPase KRas isoform X1 [KO:K07827]
100483990  NOS3; nitric oxide synthase, endothelial isoform X2 [KO:K13242] [EC:1.14.13.39]
100484344  BCL2; LOW QUALITY PROTEIN: apoptosis regulator Bcl-2 [KO:K02161]
100484518  ESR1; estrogen receptor isoform X1 [KO:K08550]
100484519  [KO:K02183]
100484531  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
100484770  [KO:K02183]
100484933  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
105234358  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
117799706  [KO:K02183]
117800432  [KO:K01403] [EC:3.4.24.35]
117800506  [KO:K03283]
117803466  [KO:K04079]
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
aml04010  MAPK signaling pathway
aml04020  Calcium signaling pathway
aml04151  PI3K-Akt signaling pathway
aml04270  Vascular smooth muscle contraction
aml04727  GABAergic synapse
aml04913  Ovarian steroidogenesis
KO pathway
ko04915   

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