KEGG   PATHWAY: pon04915
Entry
pon04915                    Pathway                                
Name
Estrogen signaling pathway - Pongo abelii (Sumatran orangutan)
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
pon04915  Estrogen signaling pathway
pon04915

Other DBs
GO: 0030520
Organism
Pongo abelii (Sumatran orangutan) [GN:pon]
Gene
100441912  ESR1; estrogen receptor isoform X2 [KO:K08550]
100459579  ESR2; estrogen receptor beta isoform X1 [KO:K08551]
100173428  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
100173221  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
100445801  LOW QUALITY PROTEIN: putative heat shock protein HSP 90-alpha A5 [KO:K04079]
100447247  heat shock protein HSP 90-beta-like [KO:K04079]
100174651  HSP90B1; endoplasmin precursor [KO:K09487]
100449665  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
100171536  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
100458051  heat shock 70 kDa protein 1-like [KO:K03283]
100172711  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
100454739  HSPA6; heat shock 70 kDa protein 6 [KO:K03283]
100172826  HSPA1A; heat shock 70 kDa protein 1 [KO:K03283]
103890872  heat shock 70 kDa protein 1 [KO:K03283]
100432710  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
100458310  NCOA2; nuclear receptor coactivator 2 [KO:K11255]
100432859  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
100938429  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
100452600  EBAG9; receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
100462638  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
100458859  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
100459844  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
100460216  KRT23; keratin, type I cytoskeletal 23 isoform X2 [KO:K07604]
100461205  KRT10; keratin, type I cytoskeletal 10 isoform X1 [KO:K07604]
100461575  KRT28; keratin, type I cytoskeletal 28 [KO:K07604]
100461945  KRT26; keratin, type I cytoskeletal 26 [KO:K07604]
100431223  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
100431591  keratin, type I cytoskeletal 24 [KO:K07604]
100442479  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
100444315  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
100443946  keratin, type I cuticular Ha8 [KO:K07604]
100444677  KRT37; keratin, type I cuticular Ha7 [KO:K07604]
100445036  keratin, type I cuticular Ha7-like [KO:K07604]
100445403  KRT34; keratin, type I cuticular Ha4 isoform X1 [KO:K07604]
100442854  keratin, type I cuticular Ha3-II isoform X1 [KO:K07604]
100443218  KRT33A; keratin, type I cuticular Ha3-I isoform X1 [KO:K07604]
100455917  KRT9; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 9 [KO:K07604]
100455304  KRT14; keratin, type I cytoskeletal 14 [KO:K07604]
100173010  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
100448380  KRT16; keratin, type I cytoskeletal 16 [KO:K07604]
100448739  KRT36; keratin, type I cuticular Ha6 isoform X1 [KO:K07604]
100460838  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
100435730  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
100938148  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 17 [KO:K07604]
103888511  KRT27; keratin, type I cytoskeletal 27 [KO:K07604]
103892845  KRT15; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 15 [KO:K07604]
100458443  KRT13; keratin, type I cytoskeletal 13 isoform X1 [KO:K07604]
112128487  KRT31; keratin, type I cuticular Ha1 isoform X1 [KO:K07604]
112129662  KRT17; keratin, type I cytoskeletal 17 [KO:K07604]
100459220  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 17-like [KO:K07604]
100435587  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 17-like [KO:K07604]
100436483  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 24 [KO:K07604]
100443406  keratin, type I cytoskeletal 17-like [KO:K07604]
112131869  keratin, type I cytoskeletal 17-like [KO:K07604]
100172401  CTSD; cathepsin D precursor [KO:K01379] [EC:3.4.23.5]
100461062  GREB1; protein GREB1 isoform X1 [KO:K27477]
100452689  TFF1; trefoil factor 1 [KO:K22456]
100454831  PGR; progesterone receptor isoform X1 [KO:K08556]
100172994  TGFA; protransforming growth factor alpha precursor [KO:K08774]
100439672  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
100462290  FOS; proto-oncogene c-Fos [KO:K04379]
100450292  JUN; transcription factor AP-1 [KO:K04448]
100440745  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
112131300  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
100442753  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X3 [KO:K04632]
103888841  neuroendocrine secretory protein 55 [KO:K04632]
100436498  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
100451667  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
100455867  MMP9; LOW QUALITY PROTEIN: matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
100437870  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
100449504  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
100445431  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
100431221  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
100460806  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
100454138  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
100438178  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
100436577  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
100461383  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
103889530  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
100174748  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform 2 [KO:K04345] [EC:2.7.11.11]
100431906  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma isoform X1 [KO:K04345] [EC:2.7.11.11]
100437102  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100294619  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
100450554  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
100462459  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100431578  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
100432292  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
100436186  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
100438869  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
100127093  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
100441756  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
100439720  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
100172895  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
100459280  EGFR; epidermal growth factor receptor isoform X2 [KO:K04361] [EC:2.7.10.1]
100173225  SHC1; SHC-transforming protein 1 [KO:K06279]
100445042  SHC2; SHC-transforming protein 2 [KO:K17447]
100462011  SHC3; SHC-transforming protein 3 [KO:K17448]
100431574  SHC4; SHC-transforming protein 4 [KO:K17449]
100173972  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100434331  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
100458733  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
100459427  HRAS; GTPase HRas [KO:K02833]
100462513  KRAS; GTPase KRas isoform X1 [KO:K07827]
100174317  NRAS; GTPase NRas precursor [KO:K07828]
100173732  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
100446021  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100450988  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100169740  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
100431824  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100432846  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100453779  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103889133  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100174298  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100173589  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
100437617  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100454279  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100448114  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100442100  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100172928  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 [KO:K04615]
100448699  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
100456074  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
100172679  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
100458137  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
100454626  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
100451674  KCNJ3; G protein-activated inward rectifier potassium channel 1 [KO:K04997]
100174134  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
100442457  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
100446377  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
100460464  POMC; pro-opiomelanocortin [KO:K05228]
100446330  OPRM1; mu-type opioid receptor isoform X8 [KO:K04215]
100452668  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
100458686  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
100458716  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
100460060  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
100434502  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
100461961  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
100445922  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
100434318  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
100434127  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
100436432  CALML5; calmodulin-like protein 5 [KO:K02183]
100436811  CALML3; calmodulin-like protein 3 [KO:K02183]
100444426  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
100172680  CALM1; calmodulin [KO:K02183]
100173214  CALM2; calmodulin [KO:K02183]
100172890  CALM3; calmodulin [KO:K02183]
100451658  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
100455662  calmodulin-alpha-like [KO:K02183]
103892390  calmodulin-like [KO:K02183]
100447953  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
100451342  GRM1; metabotropic glutamate receptor 1 isoform X3 [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
pon04010  MAPK signaling pathway
pon04020  Calcium signaling pathway
pon04151  PI3K-Akt signaling pathway
pon04270  Vascular smooth muscle contraction
pon04727  GABAergic synapse
pon04913  Ovarian steroidogenesis
KO pathway
ko04915   
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