KEGG   PATHWAY: cdk04915
Entry
cdk04915                    Pathway                                
Name
Estrogen signaling pathway - Camelus dromedarius (Arabian 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
cdk04915  Estrogen signaling pathway
cdk04915

Other DBs
GO: 0030520
Organism
Camelus dromedarius (Arabian camel) [GN:cdk]
Gene
105100955  ESR1; LOW QUALITY PROTEIN: estrogen receptor [KO:K08550]
105086199  ESR2; estrogen receptor beta isoform X1 [KO:K08551]
105088639  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
105103462  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
105097473  HSP90B1; endoplasmin [KO:K09487]
105101346  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 isoform X1 [KO:K09571] [EC:5.2.1.8]
105102944  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
105087446  LOW QUALITY PROTEIN: heat shock 70 kDa protein 1B [KO:K03283]
105087447  heat shock 70 kDa protein 1-like isoform X1 [KO:K03283]
105094503  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
105105187  HSPA6; heat shock 70 kDa protein 6 [KO:K03283]
116147648  heat shock 70 kDa protein 1B [KO:K03283]
105100028  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
105103892  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
105087857  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
105088999  BCL2; LOW QUALITY PROTEIN: apoptosis regulator Bcl-2 [KO:K02161]
105093294  EBAG9; receptor-binding cancer antigen expressed on SiSo cells isoform X2 [KO:K22455]
105085238  KRT10; keratin, type I cytoskeletal 10 [KO:K07604]
105085240  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
105085241  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
105085242  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
105085244  KRT28; keratin, type I cytoskeletal 28 [KO:K07604]
105085245  keratin, type I cytoskeletal 27 [KO:K07604]
105085246  keratin, type I cytoskeletal 25 [KO:K07604]
105085249  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
105085250  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
105085251  KRT26; keratin, type I cytoskeletal 26 isoform X1 [KO:K07604]
105094047  keratin, type I cuticular Ha1-like [KO:K07604]
105094048  keratin, type I cuticular Ha3-I [KO:K07604]
105094049  keratin, type I cuticular Ha3-I-like [KO:K07604]
105094051  KRT15; keratin, type I cytoskeletal 15 isoform X1 [KO:K07604]
105094052  keratin, type I cytoskeletal 13 [KO:K07604]
105094054  KRT36; keratin, type I cuticular Ha6 isoform X1 [KO:K07604]
105094055  KRT35; keratin, type I cuticular Ha5 isoform X2 [KO:K07604]
105094056  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
105094057  keratin, type I cytoskeletal 14 [KO:K07604]
105094058  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 42-like [KO:K07604]
105094059  KRT17; keratin, type I cytoskeletal 17 isoform X2 [KO:K07604]
105094069  keratin, type I cuticular Ha3-I [KO:K07604]
105094072  KRT9; keratin, type I cytoskeletal 9 [KO:K07604]
105094581  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
105099065  KRT24; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 24 [KO:K07604]
105105228  CTSD; cathepsin D isoform X1 [KO:K01379] [EC:3.4.23.5]
105091260  GREB1; protein GREB1 isoform X1 [KO:K27477]
105101666  TFF1; trefoil factor 1 [KO:K22456]
105087195  PGR; LOW QUALITY PROTEIN: progesterone receptor [KO:K08556]
105088937  TGFA; protransforming growth factor alpha [KO:K08774]
105099020  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
105086086  FOS; proto-oncogene c-Fos [KO:K04379]
105092850  JUN; LOW QUALITY PROTEIN: transcription factor AP-1 [KO:K04448]
105094564  SP1; transcription factor Sp1 [KO:K04684]
105105866  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
105095656  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
105095655  neuroendocrine secretory protein 55 [KO:K04632]
105084996  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
105097506  MMP2; 72 kDa type IV collagenase isoform X1 [KO:K01398] [EC:3.4.24.24]
105087845  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
105098108  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
105095715  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
105094039  ADCY2; LOW QUALITY PROTEIN: adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
105100030  ADCY3; adenylate cyclase type 3 isoform X5 [KO:K08043] [EC:4.6.1.1]
105102432  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
105090284  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
105103816  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
105097528  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
105096450  ADCY8; adenylate cyclase type 8 isoform X2 [KO:K08048] [EC:4.6.1.1]
105099828  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
105095035  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105100776  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
105093562  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X2 [KO:K05870]
105097571  ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
105091928  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105089327  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
105106926  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
105105303  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
105091622  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
105102288  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
105095833  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
105090854  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
105105749  EGFR; LOW QUALITY PROTEIN: epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
105089005  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
105093416  SHC2; LOW QUALITY PROTEIN: SHC-transforming protein 2 [KO:K17447]
105086410  SHC3; LOW QUALITY PROTEIN: SHC-transforming protein 3 [KO:K17448]
105104832  SHC4; SHC-transforming protein 4 [KO:K17449]
105104642  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
105091467  SOS2; LOW QUALITY PROTEIN: son of sevenless homolog 2 [KO:K03099]
105103654  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
105105427  HRAS; GTPase HRas isoform X1 [KO:K02833]
105100066  KRAS; GTPase KRas isoform X1 [KO:K07827]
105089630  NRAS; GTPase NRas [KO:K07828]
105093099  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105093267  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105105302  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
105095214  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105102769  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105086305  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
105107003  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
105085928  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105084758  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
105101867  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
105092913  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
105099264  AKT3; RAC-gamma serine/threonine-protein kinase isoform X3 [KO:K04456] [EC:2.7.11.1]
105104845  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105093393  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105086898  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 isoform X2 [KO:K04615]
105101142  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
105087520  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
105085647  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
105100375  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
105096168  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
105093719  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
105103945  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
105100147  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
105094272  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
105100044  POMC; pro-opiomelanocortin [KO:K05228]
105100935  OPRM1; mu-type opioid receptor [KO:K04215]
105093214  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
105087414  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
105101292  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
105101500  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
105101545  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X4 [KO:K05858] [EC:3.1.4.11]
105096910  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
105093156  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X2 [KO:K04958]
105102013  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
105101373  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
105096001  CALM1; calmodulin-1 [KO:K02183]
105093281  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
105104026  CALM3; calmodulin-3 [KO:K02183]
105105602  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
105092364  CALM2; calmodulin-2 [KO:K02183]
116147086  calmodulin-like [KO:K02183]
105105831  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
105092074  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
cdk04010  MAPK signaling pathway
cdk04020  Calcium signaling pathway
cdk04151  PI3K-Akt signaling pathway
cdk04270  Vascular smooth muscle contraction
cdk04727  GABAergic synapse
cdk04913  Ovarian steroidogenesis
KO pathway
ko04915   
LinkDB

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