KEGG   PATHWAY: mnp04915
Entry
mnp04915                    Pathway                                
Name
Estrogen signaling pathway - Mustela nigripes (black-footed ferret)
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
mnp04915  Estrogen signaling pathway
mnp04915

Other DBs
GO: 0030520
Organism
Mustela nigripes (black-footed ferret) [GN:mnp]
Gene
132018399  ESR1; estrogen receptor [KO:K08550]
132000023  ESR2; estrogen receptor beta [KO:K08551]
132000270  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
132023924  LOW QUALITY PROTEIN: heat shock protein HSP 90-alpha-like [KO:K04079]
132018009  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
132013588  LOW QUALITY PROTEIN: heat shock protein HSP 90-alpha-like [KO:K04079]
132019308  HSP90B1; endoplasmin [KO:K09487]
132017914  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 isoform X1 [KO:K09571] [EC:5.2.1.8]
132019967  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
132017812  HSPA1L; heat shock 70 kDa protein 1-like [KO:K03283]
132017813  heat shock 70 kDa protein 1-like [KO:K03283]
132017814  heat shock 70 kDa protein 1 [KO:K03283]
132026749  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
132027862  heat shock cognate 71 kDa protein-like [KO:K03283]
132013920  heat shock cognate 71 kDa protein-like [KO:K03283]
132021182  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
132014071  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
132022000  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
132023669  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
132014242  EBAG9; receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
132008647  keratin, type I cuticular Ha3-I [KO:K07604]
132009214  keratin, type I cuticular Ha1-like [KO:K07604]
132003111  keratin, type I cytoskeletal 26-like [KO:K07604]
132003211  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
132003424  KRT15; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 15 [KO:K07604]
132003425  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
132003509  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
132003550  keratin, type I cytoskeletal 27 [KO:K07604]
132003653  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
132003791  KRT10; keratin, type I cytoskeletal 10 [KO:K07604]
132003792  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
132003793  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
132004118  keratin, type I cytoskeletal 42 [KO:K07604]
132004119  KRT9; keratin, type I cytoskeletal 9 [KO:K07604]
132004120  keratin, type I cuticular Ha7-like [KO:K07604]
132004121  keratin, type I cuticular Ha8-like [KO:K07604]
132004123  keratin, type I cuticular Ha1-like [KO:K07604]
132004251  keratin, type I cytoskeletal 17 [KO:K07604]
132004309  keratin, type I cytoskeletal 14 [KO:K07604]
132004347  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
132004351  keratin, type I cytoskeletal 16 [KO:K07604]
132004392  keratin, type I cuticular Ha6 [KO:K07604]
132004409  keratin, type I cytoskeletal 13 [KO:K07604]
132004411  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
132004436  keratin, type I cuticular Ha8-like [KO:K07604]
132004467  KRT24; keratin, type I cytoskeletal 24 [KO:K07604]
132004485  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
132004490  KRT28; keratin, type I cytoskeletal 28 [KO:K07604]
132012192  keratin, type I cytoskeletal 18-like [KO:K07604]
132019714  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
131998884  keratin, type I cytoskeletal 18-like [KO:K07604]
132016741  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
132021143  GREB1; protein GREB1 [KO:K27477]
132010355  TFF1; trefoil factor 1 [KO:K22456]
132012183  PGR; progesterone receptor isoform X1 [KO:K08556]
132021470  TGFA; protransforming growth factor alpha [KO:K08774]
132004211  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
132000157  FOS; protein c-Fos [KO:K04379]
132000935  JUN; transcription factor Jun [KO:K04448]
132019731  SP1; transcription factor Sp1 [KO:K04684]
132027138  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
132022829  neuroendocrine secretory protein 55 [KO:K04632]
132022063  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like [KO:K04632]
132022064  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
132021907  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
132004844  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
132021985  MMP9; matrix metalloproteinase-9 isoform X1 [KO:K01403] [EC:3.4.24.35]
132028585  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
132016088  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
132028199  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
132021183  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
131999850  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
132011863  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
132019632  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
132005324  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
132014306  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
132026955  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
132001064  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
132011072  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
132013496  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
132013851  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
132009003  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
132019205  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
132008271  cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
132008517  cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
132015669  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
132009653  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
132024618  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
132025947  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
132015844  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
132017831  ATF6B; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
132016105  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
132025921  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
132010667  SHC2; SHC-transforming protein 2 [KO:K17447]
132024896  SHC3; SHC-transforming protein 3 [KO:K17448]
131999737  SHC4; SHC-transforming protein 4 [KO:K17449]
132003151  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
132021307  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
131999927  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
132016391  HRAS; GTPase HRas isoform X1 [KO:K02833]
132027717  LOW QUALITY PROTEIN: ras protein let-60-like [KO:K02833]
132019561  KRAS; GTPase KRas isoform X1 [KO:K07827]
132001334  NRAS; GTPase NRas [KO:K07828]
132002077  LOW QUALITY PROTEIN: GTPase NRas-like [KO:K07828]
132011570  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
131999543  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
132010799  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
132008541  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
132023779  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
132026755  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
132001008  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
132010495  PIK3CB; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
132012033  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
132000809  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
132011173  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
132028693  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
132000311  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
132025379  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
132005674  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
132024571  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
132017739  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
132001262  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
132015994  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
132011347  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
132005670  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
132013755  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
132012398  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
132025794  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
132012254  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
132022244  POMC; pro-opiomelanocortin [KO:K05228]
132018410  OPRM1; mu-type opioid receptor [KO:K04215]
132011420  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
132024788  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
132019538  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
131999626  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
132021732  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
132021734  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
132011514  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
132019550  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
132017890  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
132015160  calmodulin-1-like [KO:K02183]
132002170  CALML6; calmodulin-like protein 6 [KO:K02183]
132005201  CALM3; calmodulin-3 [KO:K02183]
132020019  calmodulin-like protein 3 [KO:K02183]
132020856  calmodulin-like [KO:K02183]
131999557  CALML4; calmodulin-like protein 4 [KO:K02183]
132021617  CALM2; calmodulin-2 [KO:K02183]
132000098  CALM1; calmodulin-1 [KO:K02183]
132015570  NOS3; nitric oxide synthase 3 isoform X1 [KO:K13242] [EC:1.14.13.39]
132018219  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
mnp04010  MAPK signaling pathway
mnp04020  Calcium signaling pathway
mnp04151  PI3K-Akt signaling pathway
mnp04270  Vascular smooth muscle contraction
mnp04727  GABAergic synapse
mnp04913  Ovarian steroidogenesis
KO pathway
ko04915   
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