KEGG   PATHWAY: panu04915
Entry
panu04915                   Pathway                                
Name
Estrogen signaling pathway - Papio anubis (olive baboon)
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
panu04915  Estrogen signaling pathway
panu04915

Other DBs
GO: 0030520
Organism
Papio anubis (olive baboon) [GN:panu]
Gene
100303417  ESR1; estrogen receptor [KO:K08550]
100303418  ESR2; estrogen receptor beta [KO:K08551]
101000592  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
101008161  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
101015403  HSP90B1; endoplasmin [KO:K09487]
101024951  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 isoform X1 [KO:K09571] [EC:5.2.1.8]
101017463  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 isoform X1 [KO:K09571] [EC:5.2.1.8]
101009582  HSPA6; LOW QUALITY PROTEIN: heat shock 70 kDa protein 6 [KO:K03283]
101024987  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
101007720  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
101011914  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
101022945  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
101026183  BCL2; apoptosis regulator Bcl-2 isoform X3 [KO:K02161]
101020820  EBAG9; receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
101009343  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
101000001  KRT10; keratin, type I cytoskeletal 10 isoform X1 [KO:K07604]
101002328  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
101020775  keratin, type I cuticular Ha7-like [KO:K07604]
101001389  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
101008727  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 18 [KO:K07604]
101021109  LOW QUALITY PROTEIN: keratin, type I cuticular Ha8 [KO:K07604]
100999656  LOW QUALITY PROTEIN: keratin, type I cuticular Ha7 [KO:K07604]
103878840  LOW QUALITY PROTEIN: keratin, type I cuticular Ha1 [KO:K07604]
101024054  KRT24; keratin, type I cytoskeletal 24 [KO:K07604]
101024763  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
101025458  KRT27; keratin, type I cytoskeletal 27 [KO:K07604]
101025821  KRT28; keratin, type I cytoskeletal 28 [KO:K07604]
101026522  KRT14; keratin, type I cytoskeletal 14 [KO:K07604]
101026880  KRT17; keratin, type I cytoskeletal 17 [KO:K07604]
100997193  KRT13; keratin, type I cytoskeletal 13 [KO:K07604]
100997536  KRT33B; keratin, type I cuticular Ha3-II [KO:K07604]
100997890  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
100998247  keratin, type I cuticular Ha3-I [KO:K07604]
100998586  KRT15; keratin, type I cytoskeletal 15 [KO:K07604]
100998928  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
100999289  KRT34; keratin, type I cuticular Ha4 [KO:K07604]
101000349  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
101000697  KRT16; keratin, type I cytoskeletal 16 isoform X2 [KO:K07604]
101001045  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
101002673  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
101003021  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
101021473  KRT9; keratin, type I cytoskeletal 9 [KO:K07604]
101001725  KRT23; keratin, type I cytoskeletal 23 isoform X1 [KO:K07604]
101025115  KRT26; keratin, type I cytoskeletal 26 [KO:K07604]
101010008  keratin, type I cytoskeletal 18 [KO:K07604]
100137367  CTSD; cathepsin D precursor [KO:K01379] [EC:3.4.23.5]
101005311  GREB1; protein GREB1 isoform X1 [KO:K27477]
101014487  TFF1; trefoil factor 1 [KO:K22456]
100303420  PGR; progesterone receptor [KO:K08556]
101023802  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
101019389  RARA; retinoic acid receptor alpha isoform X2 [KO:K08527]
101021141  FOS; proto-oncogene c-Fos isoform X1 [KO:K04379]
101010894  JUN; transcription factor AP-1 [KO:K04448]
116268873  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
101001376  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
103887915  neuroendocrine secretory protein 55 [KO:K04632]
101006785  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X2 [KO:K04632]
101025530  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
101014166  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
101003884  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
101005723  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
100998237  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
101006754  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
101006469  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
101021139  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
101014828  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
101008785  ADCY6; adenylate cyclase type 6 isoform X3 [KO:K08046] [EC:4.6.1.1]
101000833  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
101007115  ADCY8; adenylate cyclase type 8 isoform X3 [KO:K08048] [EC:4.6.1.1]
101004325  ADCY9; adenylate cyclase type 9 isoform X2 [KO:K08049] [EC:4.6.1.1]
101026251  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X15 [KO:K04345] [EC:2.7.11.11]
101026282  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
101020553  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X2 [KO:K04345] [EC:2.7.11.11]
101011350  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
101013627  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101017891  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
101004296  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
101020406  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
101004434  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
101008452  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
101007514  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X4 [KO:K09047]
101003588  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
101001939  SHC1; SHC-transforming protein 1 isoform X2 [KO:K06279]
101006054  LOW QUALITY PROTEIN: SHC-transforming protein 2 [KO:K17447]
101024393  SHC3; SHC-transforming protein 3 [KO:K17448]
116272720  SHC-transforming protein 4-like [KO:K17449]
116272724  SHC-transforming protein 4-like [KO:K17449]
116272729  SHC-transforming protein 4-like [KO:K17449]
116272733  SHC-transforming protein 4-like [KO:K17449]
116272789  SHC-transforming protein 4 [KO:K17449]
101014651  SHC-transforming protein 4 [KO:K17449]
101002675  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
101022024  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
101003749  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
101002992  HRAS; GTPase HRas isoform X2 [KO:K02833]
101017528  KRAS; GTPase KRas isoform X2 [KO:K07827]
101026253  NRAS; GTPase NRas isoform X2 [KO:K07828]
101009029  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101008394  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
101004074  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
101012041  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101006756  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
101004976  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101008699  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101002278  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
100510873  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X4 [KO:K02649]
101009981  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101002971  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100997634  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101000402  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100381179  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101011518  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
101021210  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 isoform X1 [KO:K04615]
101011013  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
101011251  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
101020528  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
101018328  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X2 [KO:K04534]
100999253  KCNJ3; G protein-activated inward rectifier potassium channel 1 [KO:K04997]
101007744  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
103877135  KCNJ9; G protein-activated inward rectifier potassium channel 3 isoform X3 [KO:K05002]
101001253  KCNJ5; G protein-activated inward rectifier potassium channel 4 isoform X3 [KO:K04999]
101008794  POMC; pro-opiomelanocortin [KO:K05228]
101002337  OPRM1; mu-type opioid receptor isoform X1 [KO:K04215]
101003920  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
101024177  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X2 [KO:K04634]
101012903  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
100998763  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
100999120  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X5 [KO:K05858] [EC:3.1.4.11]
101010000  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X4 [KO:K05858] [EC:3.1.4.11]
101017317  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
101023200  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
101001272  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
101017532  CALML6; calmodulin-like protein 6 [KO:K02183]
100997835  CALML5; calmodulin-like protein 5 [KO:K02183]
100997036  CALM2; calmodulin-2 [KO:K02183]
101019754  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
101007101  CALM1; calmodulin-1 isoform X1 [KO:K02183]
101011767  CALM3; calmodulin-3 isoform X2 [KO:K02183]
100998530  CALML3; calmodulin-like protein 3 [KO:K02183]
101024888  NOS3; LOW QUALITY PROTEIN: nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
101005483  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
panu04010  MAPK signaling pathway
panu04020  Calcium signaling pathway
panu04151  PI3K-Akt signaling pathway
panu04270  Vascular smooth muscle contraction
panu04727  GABAergic synapse
panu04913  Ovarian steroidogenesis
KO pathway
ko04915   
LinkDB

DBGET integrated database retrieval system