KEGG   PATHWAY: cbai04915
Entry
cbai04915                   Pathway                                
Name
Estrogen signaling pathway - Camelus bactrianus (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
cbai04915  Estrogen signaling pathway
cbai04915

Other DBs
GO: 0030520
Organism
Camelus bactrianus (Bactrian camel) [GN:cbai]
Gene
105077329  ESR1; estrogen receptor [KO:K08550]
105074660  ESR2; estrogen receptor beta [KO:K08551]
105079942  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
105083823  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
105081297  HSP90B1; endoplasmin [KO:K09487]
105076394  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
105064184  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
105078638  HSPA8; LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein [KO:K03283]
105068023  HSPA6; heat shock 70 kDa protein 6 [KO:K03283]
105074047  heat shock 70 kDa protein 1B-like [KO:K03283]
105074048  HSPA1B; LOW QUALITY PROTEIN: heat shock 70 kDa protein 1A/1B [KO:K03283]
105074049  HSPA1L; heat shock 70 kDa protein 1-like [KO:K03283]
105063876  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
105078564  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
105071872  NCOA3; LOW QUALITY PROTEIN: nuclear receptor coactivator 3 [KO:K11256] [EC:2.3.1.48]
105073903  BCL2; LOW QUALITY PROTEIN: apoptosis regulator Bcl-2 [KO:K02161]
105069663  EBAG9; receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
105076272  KRT18; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 18 [KO:K07604]
105079320  keratin, type I cuticular Ha3-I [KO:K07604]
105079321  keratin, type I cuticular Ha3-I-like [KO:K07604]
105079323  keratin, type I microfibrillar 48 kDa, component 8C-1 [KO:K07604]
105079324  KRT15; keratin, type I cytoskeletal 15 [KO:K07604]
105079325  KRT13; keratin, type I cytoskeletal 13 [KO:K07604]
105079326  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
105079327  keratin, type I cytoskeletal 19-like [KO:K07604]
105079328  keratin, type I cytoskeletal 14 [KO:K07604]
105079329  KRT17; keratin, type I cytoskeletal 17 [KO:K07604]
105079331  keratin, type I cytoskeletal 42 [KO:K07604]
105079339  keratin, type I cuticular Ha4-like [KO:K07604]
105079342  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
105073216  KRT10; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 10 [KO:K07604]
105073217  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
105073218  KRT20; keratin, type I cytoskeletal 20 isoform X1 [KO:K07604]
105073219  KRT23; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 23 [KO:K07604]
105073220  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
105073221  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
105073224  KRT28; keratin, type I cytoskeletal 28 [KO:K07604]
105073225  KRT27; keratin, type I cytoskeletal 27 [KO:K07604]
105073227  KRT26; keratin, type I cytoskeletal 26 [KO:K07604]
105073228  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
105073329  KRT24; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 24 [KO:K07604]
105070396  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
105076047  GREB1; protein GREB1 [KO:K27477]
105083583  PGR; LOW QUALITY PROTEIN: progesterone receptor [KO:K08556]
105075786  TGFA; protransforming growth factor alpha [KO:K08774]
105073239  RARA; retinoic acid receptor alpha [KO:K08527]
105075289  FOS; proto-oncogene c-Fos [KO:K04379]
105071674  JUN; transcription factor AP-1 [KO:K04448]
105076285  SP1; transcription factor Sp1 [KO:K04684]
105077878  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
105071802  guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
105071803  neuroendocrine secretory protein 55 [KO:K04632]
105073493  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
105075731  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
105071885  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
105082198  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
105080525  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
105081234  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
105063873  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
105068818  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
105081635  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
105076187  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
105074271  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
105082946  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
105064797  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
105075498  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105068302  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
105072963  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
105073454  ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
105073101  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105076770  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
105078379  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
105068196  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
105063046  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
105067333  CREB3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3 [KO:K09048]
105082021  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
105074031  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
105067674  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
105068173  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
105078342  SHC2; SHC-transforming protein 2 [KO:K17447]
105065419  SHC3; SHC-transforming protein 3 [KO:K17448]
105077007  SHC4; SHC-transforming protein 4 [KO:K17449]
105065653  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
105078489  SOS2; son of sevenless homolog 2 [KO:K03099]
105078987  SOS1; son of sevenless homolog 1 [KO:K03099]
105069943  HRAS; GTPase HRas isoform X1 [KO:K02833]
105062297  KRAS; GTPase KRas [KO:K07827]
105079555  NRAS; GTPase NRas [KO:K07828]
105067475  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105069422  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105078209  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105082839  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105069349  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105063312  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105071167  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
105066839  PIK3CB; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
105082679  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105064416  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
105065663  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
105079975  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105083596  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105062855  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105084061  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 [KO:K04615]
105067386  GABBR2; LOW QUALITY PROTEIN: gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
105080234  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
105062385  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
105063651  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
105078712  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
105081914  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
105072485  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
105069587  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
105071238  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
105077337  OPRM1; mu-type opioid receptor isoform X1 [KO:K04215]
105080156  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
105067298  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
105077045  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
105082996  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
105082997  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
105070632  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
105074761  ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
105062304  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
105064212  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
105074723  calmodulin-like [KO:K02183]
105079857  CALM1; calmodulin [KO:K02183]
105079032  CALM2; calmodulin [KO:K02183]
105062547  CALM3; calmodulin [KO:K02183]
105069522  CALML4; calmodulin-like protein 4 [KO:K02183]
105071194  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
105067010  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
105077300  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
cbai04010  MAPK signaling pathway
cbai04020  Calcium signaling pathway
cbai04151  PI3K-Akt signaling pathway
cbai04270  Vascular smooth muscle contraction
cbai04727  GABAergic synapse
cbai04913  Ovarian steroidogenesis
KO pathway
ko04915   
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