KEGG   PATHWAY: pyu04915
Entry
pyu04915                    Pathway                                
Name
Estrogen signaling pathway - Herpailurus yagouaroundi (jaguarundi)
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
pyu04915  Estrogen signaling pathway
pyu04915

Other DBs
GO: 0030520
Organism
Herpailurus yagouaroundi (jaguarundi) [GN:pyu]
Gene
121010805  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
121011002  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
121011233  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
121011444  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
121011871  [KO:K03283]
121012072  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
121012098  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
121012223  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
121012476  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
121012479  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
121013290  OPRM1; mu-type opioid receptor [KO:K04215]
121013301  ESR1; estrogen receptor isoform X1 [KO:K08550]
121013347  GRM1; metabotropic glutamate receptor 1 isoform X1 [KO:K04603]
121013551  SHC3; SHC-transforming protein 3 [KO:K17448]
121013601  [KO:K04634]
121014090  PRKACA; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
121014870  [KO:K02183]
121014873  [KO:K02183]
121014969  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
121015111  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
121015443  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
121015654  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
121015682  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
121016318  CALM2; calmodulin-2 [KO:K02183]
121016847  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
121016977  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
121017018  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
121017477  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
121017912  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
121018400  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 [KO:K04615]
121018659  CALM3; calmodulin-3 isoform X1 [KO:K02183]
121019131  TGFA; protransforming growth factor alpha [KO:K08774]
121019338  CALML6; calmodulin-like protein 6 [KO:K02183]
121019600  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
121019943  [KO:K04632]
121019944  [KO:K04632]
121020585  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
121021362  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
121021465  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
121021890  SHC2; SHC-transforming protein 2 [KO:K17447]
121022022  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
121022226  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
121022360  HSPA1L; heat shock 70 kDa protein 1-like [KO:K03283]
121022388  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
121022826  HRAS; GTPase HRas isoform X1 [KO:K02833]
121022952  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
121023018  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
121023937  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
121023963  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
121025238  [KO:K03283]
121026457  [KO:K03283]
121026473  [KO:K03283]
121026480  [KO:K07604]
121026484  [KO:K07604]
121027050  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
121027214  JUN; transcription factor AP-1 [KO:K04448]
121027378  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
121027636  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
121027738  NRAS; GTPase NRas [KO:K07828]
121028276  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
121028557  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
121028803  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
121029298  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
121029340  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
121029518  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
121030576  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
121030728  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
121030939  [KO:K03283]
121030974  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
121031569  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
121031737  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
121031889  ESR2; estrogen receptor beta [KO:K08551]
121032071  FOS; proto-oncogene c-Fos [KO:K04379]
121032181  CALM1; calmodulin-1 [KO:K02183]
121032306  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
121032358  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
121032687  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
121033733  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
121034018  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
121034643  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
121034724  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
121035557  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
121035634  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
121035941  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
121036101  [KO:K03283]
121036524  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
121036531  TFF1; trefoil factor 1 [KO:K22456]
121038142  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
121038490  SP1; transcription factor Sp1 [KO:K04684]
121038513  KRT18; keratin, type I cytoskeletal 18 isoform X1 [KO:K07604]
121038647  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
121038795  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
121038809  KRAS; GTPase KRas isoform X1 [KO:K07827]
121039469  PGR; progesterone receptor isoform X1 [KO:K08556]
121040318  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
121040515  HSP90B1; endoplasmin [KO:K09487]
121041241  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
121041326  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
121041495  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
121041673  SHC4; SHC-transforming protein 4 [KO:K17449]
121041863  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
121041895  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
121042416  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
121042872  EBAG9; receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
121042990  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
121043476  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
121044105  GREB1; protein GREB1 isoform X1 [KO:K27477]
121044198  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
121044199  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
121044205  POMC; pro-opiomelanocortin [KO:K05228]
121044367  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
121044935  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
121044949  KRT24; keratin, type I cytoskeletal 24 [KO:K07604]
121044950  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
121044952  [KO:K07604]
121044953  KRT10; keratin, type I cytoskeletal 10 isoform X1 [KO:K07604]
121044954  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
121044955  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
121044956  KRT27; keratin, type I cytoskeletal 27 [KO:K07604]
121044957  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
121044958  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
121044959  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
121044977  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
121044978  [KO:K07604]
121044979  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
121044980  KRT32; keratin, type I cuticular Ha2 isoform X1 [KO:K07604]
121044981  [KO:K07604]
121044982  [KO:K07604]
121044983  [KO:K07604]
121044984  [KO:K07604]
121044985  KRT15; keratin, type I cytoskeletal 15 isoform X1 [KO:K07604]
121044986  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
121044987  KRT13; keratin, type I cytoskeletal 13 [KO:K07604]
121044989  KRT9; keratin, type I cytoskeletal 9 [KO:K07604]
121044990  KRT14; keratin, type I cytoskeletal 14 [KO:K07604]
121044991  KRT16; keratin, type I cytoskeletal 16 isoform X1 [KO:K07604]
121044992  [KO:K07604]
121044993  KRT17; keratin, type I cytoskeletal 17 [KO:K07604]
121045271  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
121045318  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
121045329  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
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
pyu04010  MAPK signaling pathway
pyu04020  Calcium signaling pathway
pyu04151  PI3K-Akt signaling pathway
pyu04270  Vascular smooth muscle contraction
pyu04727  GABAergic synapse
pyu04913  Ovarian steroidogenesis
KO pathway
ko04915   

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