KEGG   PATHWAY: ncar04915
Entry
ncar04915                   Pathway                                
Name
Estrogen signaling pathway - Sciurus carolinensis (gray squirrel)
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
ncar04915  Estrogen signaling pathway
ncar04915

Other DBs
GO: 0030520
Organism
Sciurus carolinensis (gray squirrel) [GN:ncar]
Gene
124988588  estrogen receptor isoform X1 [KO:K08550]
124977901  estrogen receptor beta isoform X1 [KO:K08551]
124988389  heat shock protein HSP 90-beta [KO:K04079]
124977378  heat shock protein HSP 90-alpha [KO:K04079]
124983444  heat shock protein HSP 90-beta-like [KO:K04079]
124982611  endoplasmin [KO:K09487]
124987991  peptidyl-prolyl cis-trans isomerase FKBP5 isoform X1 [KO:K09571] [EC:5.2.1.8]
124982009  peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
124993125  heat shock 70 kDa protein 6 [KO:K03283]
124993503  heat shock cognate 71 kDa protein-like [KO:K03283]
124988136  heat shock 70 kDa protein 1-like isoform X1 [KO:K03283]
124988137  heat shock 70 kDa protein 1 [KO:K03283]
124988335  heat shock 70 kDa protein 1 [KO:K03283]
124988964  heat shock cognate 71 kDa protein [KO:K03283]
124959781  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
124962973  nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
124982328  nuclear receptor coactivator 2 isoform X1 [KO:K11255]
124970861  nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
124965545  apoptosis regulator Bcl-2 [KO:K02161]
124967534  receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
124990886  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 19-like [KO:K07604]
124978935  keratin, type I cytoskeletal 23-like [KO:K07604]
124979270  keratin, type I cytoskeletal 40-like [KO:K07604]
124979271  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 39-like [KO:K07604]
124979273  keratin, type I cytoskeletal 26-like [KO:K07604]
124979646  keratin, type I cuticular Ha4 [KO:K07604]
124979647  keratin, type I cuticular Ha1 [KO:K07604]
124979648  keratin, type I cuticular Ha3-II [KO:K07604]
124979745  keratin, type I cuticular Ha6 isoform X1 [KO:K07604]
124979808  keratin, type I cytoskeletal 15 [KO:K07604]
124979809  keratin, type I cytoskeletal 19 [KO:K07604]
124979861  keratin, type I cytoskeletal 10 isoform X1 [KO:K07604]
124979862  keratin, type I cytoskeletal 28 [KO:K07604]
124979887  keratin, type I cytoskeletal 16 [KO:K07604]
124979919  keratin, type I cuticular Ha3-I [KO:K07604]
124979924  keratin, type I cytoskeletal 13 [KO:K07604]
124979972  keratin, type I cytoskeletal 27 [KO:K07604]
124979976  keratin, type I cytoskeletal 12 [KO:K07604]
124980052  keratin, type I cytoskeletal 17 [KO:K07604]
124980053  keratin, type I cytoskeletal 42 [KO:K07604]
124980055  keratin, type I cytoskeletal 25 [KO:K07604]
124980101  keratin, type I cytoskeletal 24-like [KO:K07604]
124980679  keratin, type I cytoskeletal 20-like [KO:K07604]
124980829  keratin, type I cytoskeletal 9-like [KO:K07604]
124980884  keratin, type I cytoskeletal 14 [KO:K07604]
124982335  keratin, type I cytoskeletal 18 [KO:K07604]
124960311  cathepsin D [KO:K01379] [EC:3.4.23.5]
124963218  LOW QUALITY PROTEIN: protein GREB1-like [KO:K27477]
124993146  trefoil factor 1-like [KO:K22456]
124958802  progesterone receptor isoform X1 [KO:K08556]
124962678  protransforming growth factor alpha [KO:K08774]
124979933  retinoic acid receptor alpha isoform X1 [KO:K08527]
124977967  protein c-Fos [KO:K04379]
124991717  transcription factor Jun [KO:K04448]
124963740  LOW QUALITY PROTEIN: transcription factor Jun-like [KO:K04448]
124962851  LOW QUALITY PROTEIN: transcription factor Sp1-like [KO:K04684]
124983225  transcription factor Sp1 isoform X1 [KO:K04684]
124969818  G-protein coupled estrogen receptor 1 [KO:K04246]
124978161  neuroendocrine secretory protein 55 [KO:K04632]
124975134  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
124977049  proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
124967289  72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
124977457  matrix metalloproteinase-9-like [KO:K01403] [EC:3.4.24.35]
124987586  proheparin-binding EGF-like growth factor [KO:K08523]
124990345  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
124987010  adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
124962927  adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
124978229  LOW QUALITY PROTEIN: adenylate cyclase type 4-like [KO:K08044] [EC:4.6.1.1]
124992559  adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
124983776  adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
124966834  adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
124965096  adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
124970113  LOW QUALITY PROTEIN: adenylate cyclase type 9-like [KO:K08049] [EC:4.6.1.1]
124985819  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
124969119  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
124979032  cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
124979831  LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-2-like [KO:K04450]
124984025  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
124991113  cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
124958938  cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
124984689  cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
124969564  cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
124964377  cyclic AMP-responsive element-binding protein 3-like isoform X1 [KO:K09048]
124991182  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
124988573  cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
124990601  epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
124982298  SHC-transforming protein 1 isoform X1 [KO:K06279]
124975378  SHC-transforming protein 2-like [KO:K17447]
124965516  SHC-transforming protein 3 isoform X1 [KO:K17448]
124978227  SHC-transforming protein 4 [KO:K17449]
124980188  growth factor receptor-bound protein 2 [KO:K04364]
124977045  son of sevenless homolog 2 [KO:K03099]
124963384  son of sevenless homolog 1 isoform X1 [KO:K03099]
124974041  LOW QUALITY PROTEIN: son of sevenless homolog 2-like [KO:K03099]
124958599  GTPase HRas isoform X1 [KO:K02833]
124991017  GTPase KRas-like [KO:K07827]
124982118  GTPase KRas isoform X1 [KO:K07827]
124962389  GTPase NRas [KO:K07828]
124971006  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
124977990  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
124969568  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
124990635  LOW QUALITY PROTEIN: mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
124970294  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
124993166  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
124993330  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
124963509  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
124986648  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
124968815  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
124962260  LOW QUALITY PROTEIN: RAC-gamma serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
124976076  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124966582  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124988516  gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
124964896  gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
124992673  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
124988012  guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
124991078  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
124967520  guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
124980509  G protein-activated inward rectifier potassium channel 1 [KO:K04997]
124993028  G protein-activated inward rectifier potassium channel 2 [KO:K05000]
124990924  G protein-activated inward rectifier potassium channel 3 [KO:K05002]
124960772  G protein-activated inward rectifier potassium channel 4 isoform X1 [KO:K04999]
124963358  pro-opiomelanocortin-like [KO:K05228]
124989714  mu-type opioid receptor [KO:K04215]
124968791  protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
124964255  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
124976705  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
124959812  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
124977474  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
124972679  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
124970932  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
124983533  inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
124988553  inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
124976834  LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
124967357  calmodulin-1 [KO:K02183]
124967948  calmodulin-like protein 6 [KO:K02183]
124962006  calmodulin-like [KO:K02183]
124962112  calmodulin-A-like [KO:K02183]
124962222  calmodulin-like protein 3 [KO:K02183]
124963056  calmodulin-1 [KO:K02183]
124976085  calmodulin-1 [KO:K02183]
124990691  nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
124989681  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
ncar04010  MAPK signaling pathway
ncar04020  Calcium signaling pathway
ncar04151  PI3K-Akt signaling pathway
ncar04270  Vascular smooth muscle contraction
ncar04727  GABAergic synapse
ncar04913  Ovarian steroidogenesis
KO pathway
ko04915   
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