KEGG   PATHWAY: csyr04915
Entry
csyr04915                   Pathway                                
Name
Estrogen signaling pathway - Carlito syrichta (Philippine tarsier)
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
csyr04915  Estrogen signaling pathway
csyr04915

Other DBs
GO: 0030520
Organism
Carlito syrichta (Philippine tarsier) [GN:csyr]
Gene
103267361  ESR1; estrogen receptor isoform X1 [KO:K08550]
103265664  ESR2; estrogen receptor beta isoform X1 [KO:K08551]
103271234  HSP90AB1; heat shock protein HSP 90-beta isoform X2 [KO:K04079]
103266451  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
103266484  HSP90B1; endoplasmin isoform X2 [KO:K09487]
103255233  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
103276145  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
103260333  LOW QUALITY PROTEIN: heat shock 70 kDa protein II-like [KO:K03283]
103256412  HSPA6; heat shock 70 kDa protein 6 [KO:K03283]
103271292  LOW QUALITY PROTEIN: heat shock 70 kDa protein 1-like [KO:K03283]
103275796  heat shock cognate 71 kDa protein isoform X2 [KO:K03283]
103258643  heat shock 70 kDa protein 1-like [KO:K03283]
103258654  LOW QUALITY PROTEIN: heat shock 70 kDa protein 1-like [KO:K03283]
103262640  NCOA1; nuclear receptor coactivator 1 isoform X3 [KO:K09101] [EC:2.3.1.48]
103272916  NCOA2; nuclear receptor coactivator 2 isoform X6 [KO:K11255]
103258627  NCOA3; nuclear receptor coactivator 3 isoform X2 [KO:K11256] [EC:2.3.1.48]
103274703  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
103250318  EBAG9; receptor-binding cancer antigen expressed on SiSo cells isoform X1 [KO:K22455]
103272912  keratin, type I cytoskeletal 18 [KO:K07604]
103274493  KRT17; keratin, type I cytoskeletal 17 isoform X2 [KO:K07604]
103274494  KRT16; keratin, type I cytoskeletal 16 [KO:K07604]
103274495  KRT14; keratin, type I cytoskeletal 14 [KO:K07604]
103274496  KRT19; keratin, type I cytoskeletal 19 isoform X1 [KO:K07604]
103274497  KRT15; keratin, type I cytoskeletal 15 isoform X2 [KO:K07604]
103274499  KRT13; keratin, type I cytoskeletal 13 isoform X1 [KO:K07604]
103274500  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
103274501  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
103274502  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
103274503  keratin, type I cuticular Ha1 isoform X1 [KO:K07604]
103274505  keratin, type I cuticular Ha3-I-like [KO:K07604]
103274513  KRT9; keratin, type I cytoskeletal 9 [KO:K07604]
103274514  KRT38; keratin, type I cuticular Ha8 [KO:K07604]
103274515  keratin, type I cuticular Ha7-like [KO:K07604]
103274516  keratin, type I cuticular Ha7-like [KO:K07604]
103258101  KRT24; keratin, type I cytoskeletal 24 [KO:K07604]
103258102  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
103258103  KRT26; keratin, type I cytoskeletal 26 [KO:K07604]
103258104  KRT27; keratin, type I cytoskeletal 27 [KO:K07604]
103258105  keratin, type I cytoskeletal 28 [KO:K07604]
103258106  KRT10; keratin, type I cytoskeletal 10 [KO:K07604]
103258107  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
103258108  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
103258109  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
103258110  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
103258112  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
103251978  GREB1; protein GREB1 [KO:K27477]
103269466  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
103266527  FOS; proto-oncogene c-Fos [KO:K04379]
103274529  JUN; transcription factor AP-1 [KO:K04448]
103260226  transcription factor Sp1 [KO:K04684]
103255740  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
103251768  neuroendocrine secretory protein 55 [KO:K04632]
103255823  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
103273857  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
103272469  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
103260266  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
103258463  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
103252919  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
103262642  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
103272228  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
103254816  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
103273462  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
103259338  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
103267869  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
103273680  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
103253311  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X2 [KO:K04345] [EC:2.7.11.11]
103266092  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
103252293  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
103264952  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
103267309  ATF4; cyclic AMP-dependent transcription factor ATF-4 isoform X2 [KO:K04374]
103249547  CREB3L3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
103252136  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
103263755  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
103265465  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
103257302  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
103273492  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X2 [KO:K09047]
103271306  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X3 [KO:K09049]
103268107  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
103249998  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
103257751  SHC3; SHC-transforming protein 3 [KO:K17448]
103272388  SHC4; SHC-transforming protein 4 [KO:K17449]
103275922  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
103270607  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
103276422  SOS2; son of sevenless homolog 2 isoform X2 [KO:K03099]
103250130  HRAS; GTPase HRas isoform X1 [KO:K02833]
103263630  KRAS; GTPase KRas isoform X2 [KO:K07827]
103259236  NRAS; GTPase NRas [KO:K07828]
103263745  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X3 [KO:K04366] [EC:2.7.11.1]
103277453  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103251709  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103265435  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
103274188  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103251553  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103266233  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103276054  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
103262537  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
103272136  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
103257728  AKT1; LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103254239  RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103263958  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103255483  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 isoform X2 [KO:K04615]
103277075  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
103263431  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
103255466  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
103264772  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
103253155  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
103262382  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
103275832  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
103261119  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
103276788  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
103262651  POMC; pro-opiomelanocortin [KO:K05228]
103251814  OPRM1; mu-type opioid receptor isoform X1 [KO:K04215]
103268097  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
103258399  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
103261218  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
103257479  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
103272341  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
103275147  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
103256992  inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103261167  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103269243  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103250483  calmodulin-like isoform X3 [KO:K02183]
103255950  calmodulin-like [KO:K02183]
103257967  calmodulin-like [KO:K02183]
103252808  calmodulin isoform X1 [KO:K02183]
103261438  calmodulin-like [KO:K02183]
103264241  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
103274844  CALML6; calmodulin-like protein 6 [KO:K02183]
103268605  calmodulin isoform X3 [KO:K02183]
103275280  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
103269071  LOW QUALITY PROTEIN: metabotropic glutamate receptor 1-like [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
csyr04010  MAPK signaling pathway
csyr04020  Calcium signaling pathway
csyr04151  PI3K-Akt signaling pathway
csyr04270  Vascular smooth muscle contraction
csyr04727  GABAergic synapse
csyr04913  Ovarian steroidogenesis
KO pathway
ko04915   
LinkDB

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