KEGG   PATHWAY: cfr04915
Entry
cfr04915                    Pathway                                
Name
Estrogen signaling pathway - Camelus ferus (Wild Bactrian camel)
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
cfr04915  Estrogen signaling pathway
cfr04915

Other DBs
GO: 0030520
Organism
Camelus ferus (Wild Bactrian camel) [GN:cfr]
Gene
102519728  ESR1; estrogen receptor isoform X1 [KO:K08550]
102504310  ESR2; estrogen receptor beta isoform X3 [KO:K08551]
102516141  HSP90AA1; heat shock protein HSP 90-alpha isoform X1 [KO:K04079]
102516313  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
102517515  HSP90B1; endoplasmin [KO:K09487]
102522367  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
102507858  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 isoform X1 [KO:K09571] [EC:5.2.1.8]
102516558  HSPA6; heat shock 70 kDa protein 6 [KO:K03283]
102517440  HSPA1L; heat shock 70 kDa protein 1-like isoform X2 [KO:K03283]
102517682  heat shock 70 kDa protein 1B [KO:K03283]
102521559  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
116658237  heat shock 70 kDa protein 1B [KO:K03283]
102511907  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
102514348  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
102516884  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
102518434  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
102506925  EBAG9; receptor-binding cancer antigen expressed on SiSo cells isoform X1 [KO:K22455]
102514049  LOW QUALITY PROTEIN: keratin, type I cuticular Ha1 [KO:K07604]
102518732  keratin, type I cytoskeletal 42 isoform X1 [KO:K07604]
102513799  KRT34; LOW QUALITY PROTEIN: keratin, type I cuticular Ha4 [KO:K07604]
102516515  keratin, type I cytoskeletal 14 [KO:K07604]
102514287  KRT35; keratin, type I cuticular Ha5 isoform X2 [KO:K07604]
102515054  KRT15; keratin, type I cytoskeletal 15 isoform X1 [KO:K07604]
102513322  keratin, type I cuticular Ha3-I [KO:K07604]
102516263  KRT17; keratin, type I cytoskeletal 17 isoform X3 [KO:K07604]
102516767  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
102514784  KRT13; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 13 [KO:K07604]
102513558  keratin, type I cuticular Ha3-I isoform X1 [KO:K07604]
102514527  KRT36; keratin, type I cuticular Ha6 isoform X1 [KO:K07604]
102515179  keratin, type I cytoskeletal 26 isoform X1 [KO:K07604]
102503494  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
102518937  KRT24; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 24 [KO:K07604]
102515690  KRT10; keratin, type I cytoskeletal 10 isoform X1 [KO:K07604]
102516714  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
102516205  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
102514914  keratin, type I cytoskeletal 25 [KO:K07604]
102516963  KRT40; keratin, type I cytoskeletal 40 isoform X1 [KO:K07604]
102516463  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
106729824  KRT20; keratin, type I cytoskeletal 20 isoform X1 [KO:K07604]
102515949  keratin, type I cytoskeletal 28 [KO:K07604]
102515440  keratin, type I cytoskeletal 27 [KO:K07604]
102519489  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 18 [KO:K07604]
116669159  KRT9; keratin, type I cytoskeletal 9 [KO:K07604]
102523939  CTSD; cathepsin D isoform X1 [KO:K01379] [EC:3.4.23.5]
102516580  GREB1; LOW QUALITY PROTEIN: protein GREB1 [KO:K27477]
116657549  TFF1; trefoil factor 1 [KO:K22456]
102519168  PGR; progesterone receptor isoform X1 [KO:K08556]
102506694  TGFA; protransforming growth factor alpha [KO:K08774]
102503688  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
102519397  FOS; proto-oncogene c-Fos [KO:K04379]
102516943  JUN; transcription factor AP-1 [KO:K04448]
102520683  SP1; transcription factor Sp1 [KO:K04684]
102519542  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
102513869  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
102509921  neuroendocrine secretory protein 55 [KO:K04632]
102520048  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
102521167  MMP2; 72 kDa type IV collagenase isoform X1 [KO:K01398] [EC:3.4.24.24]
102509767  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
102510168  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
102517882  ADCY1; LOW QUALITY PROTEIN: adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
102510993  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
102512950  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
102524031  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
102503785  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
102519611  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
102524614  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
102521259  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
102505261  ADCY9; LOW QUALITY PROTEIN: adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
102508985  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102506255  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
102508765  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
102512476  ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
102508076  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
102510171  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
102516625  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
102511454  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
102516586  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X2 [KO:K09048]
102510394  CREB3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3 [KO:K09048]
102514154  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X2 [KO:K09047]
102521467  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
102504272  EGFR; LOW QUALITY PROTEIN: epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102524489  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
102506382  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
102508169  SHC3; SHC-transforming protein 3 [KO:K17448]
102517753  SHC4; SHC-transforming protein 4 [KO:K17449]
102515306  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
102507247  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
102517014  SOS2; son of sevenless homolog 2 [KO:K03099]
102524334  HRAS; GTPase HRas isoform X1 [KO:K02833]
102516372  KRAS; GTPase KRas isoform X1 [KO:K07827]
102509562  NRAS; GTPase NRas [KO:K07828]
102517521  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102515937  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102511209  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
102517586  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102521659  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102523502  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102518643  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102519994  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102513205  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
102505690  LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102520923  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
102503460  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102515350  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102519101  RAC-gamma serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
106729149  AKT1; LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102522913  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 isoform X1 [KO:K04615]
102513730  GABBR1; LOW QUALITY PROTEIN: gamma-aminobutyric acid type B receptor subunit 1 [KO:K04615]
102518290  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
102504487  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
102522331  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
102503533  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
102520891  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
102504753  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
106728853  KCNJ9; G protein-activated inward rectifier potassium channel 3 isoform X1 [KO:K05002]
102521489  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
102516898  POMC; pro-opiomelanocortin [KO:K05228]
102520916  OPRM1; mu-type opioid receptor [KO:K04215]
102511255  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
102508547  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
102509058  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X3 [KO:K05858] [EC:3.1.4.11]
102505338  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
102513996  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
102513431  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
102521814  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
102517295  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102524078  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
102512690  CALM1; calmodulin-1 [KO:K02183]
102516816  CALM3; calmodulin-3 [KO:K02183]
102509134  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
102517946  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
102512134  CALM2; calmodulin-2 [KO:K02183]
102518712  calmodulin [KO:K02183]
102524296  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
102523079  GRM1; metabotropic glutamate receptor 1 [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
cfr04010  MAPK signaling pathway
cfr04020  Calcium signaling pathway
cfr04151  PI3K-Akt signaling pathway
cfr04270  Vascular smooth muscle contraction
cfr04727  GABAergic synapse
cfr04913  Ovarian steroidogenesis
KO pathway
ko04915   
LinkDB

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