KEGG   PATHWAY: mlk04915
Entry
mlk04915                    Pathway                                
Name
Estrogen signaling pathway - Mustela lutreola (European mink)
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
mlk04915  Estrogen signaling pathway
mlk04915

Other DBs
GO: 0030520
Organism
Mustela lutreola (European mink) [GN:mlk]
Gene
131833450  ESR1; estrogen receptor [KO:K08550]
131836671  ESR2; estrogen receptor beta [KO:K08551]
131837003  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
131834029  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
131827404  LOW QUALITY PROTEIN: heat shock protein HSP 90-alpha-like [KO:K04079]
131832553  LOW QUALITY PROTEIN: heat shock protein HSP 90-alpha-like [KO:K04079]
131839347  HSP90B1; endoplasmin [KO:K09487]
131838392  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
131834198  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 isoform X1 [KO:K09571] [EC:5.2.1.8]
131837691  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
131833881  heat shock cognate 71 kDa protein-like [KO:K03283]
131834338  heat shock 70 kDa protein 1-like [KO:K03283]
131834339  heat shock 70 kDa protein 1 [KO:K03283]
131834340  heat shock 70 kDa protein 1-like [KO:K03283]
131832001  heat shock cognate 71 kDa protein-like [KO:K03283]
131807294  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
131826726  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
131807502  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
131811845  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
131826488  EBAG9; receptor-binding cancer antigen expressed on SiSo cells isoform X1 [KO:K22455]
131837257  keratin, type I cytoskeletal 18-like [KO:K07604]
131838714  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
131811659  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 15-like [KO:K07604]
131821889  keratin, type I cytoskeletal 18-like [KO:K07604]
131828781  keratin, type I cytoskeletal 18-like [KO:K07604]
131815865  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
131815866  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
131815867  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
131815868  KRT10; keratin, type I cytoskeletal 10 [KO:K07604]
131815870  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
131815871  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
131815944  KRT24; keratin, type I cytoskeletal 24 [KO:K07604]
131815950  keratin, type I cuticular Ha1 [KO:K07604]
131815953  keratin, type I cuticular Ha1-like [KO:K07604]
131815954  keratin, type I cuticular Ha3-II [KO:K07604]
131815966  keratin, type I cuticular Ha3-I [KO:K07604]
131815972  KRT38; keratin, type I cuticular Ha8 [KO:K07604]
131815989  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
131816020  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
131816025  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
131816031  KRT28; keratin, type I cytoskeletal 28 [KO:K07604]
131816034  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
131816154  keratin, type I cytoskeletal 26-like [KO:K07604]
131816496  KRT27; keratin, type I cytoskeletal 27 [KO:K07604]
131816568  keratin, type I cytoskeletal 17 [KO:K07604]
131816569  keratin, type I cytoskeletal 14 [KO:K07604]
131816571  keratin, type I cytoskeletal 15 [KO:K07604]
131816572  keratin, type I cytoskeletal 13 [KO:K07604]
131816573  keratin, type I cytoskeletal 42 isoform X1 [KO:K07604]
131816574  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
131816575  keratin, type I cytoskeletal 16 [KO:K07604]
131816665  keratin, type I cytoskeletal 18-like [KO:K07604]
131816716  KRT9; keratin, type I cytoskeletal 9 [KO:K07604]
131816717  keratin, type I cuticular Ha7-like [KO:K07604]
131816718  keratin, type I cuticular Ha8-like [KO:K07604]
131809982  keratin, type I cytoskeletal 18-like [KO:K07604]
131817810  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
131807362  GREB1; protein GREB1 isoform X1 [KO:K27477]
131825705  TFF1; trefoil factor 1 [KO:K22456]
131838919  PGR; progesterone receptor [KO:K08556]
131840269  TGFA; protransforming growth factor alpha [KO:K08774]
131816638  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
131836857  FOS; protein c-Fos [KO:K04379]
131809019  JUN; transcription factor Jun [KO:K04448]
131838694  SP1; transcription factor Sp1 [KO:K04684]
131819831  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
131840487  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like [KO:K04632]
131840488  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
131807579  neuroendocrine secretory protein 55 [KO:K04632]
131807708  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
131818062  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
131807533  MMP9; matrix metalloproteinase-9 isoform X1 [KO:K01403] [EC:3.4.24.35]
131832137  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
131829179  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
131831568  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
131807291  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
131836404  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
131824632  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
131838820  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
131818734  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
131826395  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
131819927  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
131823635  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
131808844  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
131827517  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
131827068  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
131839499  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
131818296  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
131811907  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
131812775  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
131814622  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
131823313  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
131829815  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
131829554  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
131834326  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
131829150  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
131814353  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
131823143  SHC2; SHC-transforming protein 2 [KO:K17447]
131812476  SHC3; SHC-transforming protein 3 [KO:K17448]
131836254  SHC4; SHC-transforming protein 4 [KO:K17449]
131816784  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
131836536  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
131840500  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
131818337  HRAS; GTPase HRas isoform X1 [KO:K02833]
131838926  KRAS; GTPase KRas isoform X1 [KO:K07827]
131810307  NRAS; GTPase NRas isoform X1 [KO:K07828]
131810524  LOW QUALITY PROTEIN: GTPase NRas-like [KO:K07828]
131824239  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
131835957  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
131823312  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
131811758  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
131820131  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
131809015  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
131824589  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
131824847  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
131823754  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
131832309  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
131810162  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
131837056  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
131815063  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
131817507  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
131834858  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
131812836  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
131829305  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
131823969  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
131810079  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
131818465  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
131827207  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
131825372  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
131815351  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
131838542  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
131808211  POMC; pro-opiomelanocortin [KO:K05228]
131833440  OPRM1; mu-type opioid receptor [KO:K04215]
131824034  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
131812467  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
131836105  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
131814631  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
131808069  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
131808080  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
131824160  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
131838936  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
131834230  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
131835976  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
131836771  CALM1; calmodulin-1 isoform X1 [KO:K02183]
131838058  calmodulin-like protein 3 [KO:K02183]
131839863  calmodulin-like [KO:K02183]
131808503  CALM2; calmodulin-2 [KO:K02183]
131817928  CALM3; calmodulin-3 [KO:K02183]
131810396  CALML6; calmodulin-like protein 6 [KO:K02183]
131829935  NOS3; LOW QUALITY PROTEIN: nitric oxide synthase 3 [KO:K13242] [EC:1.14.13.39]
131833708  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
mlk04010  MAPK signaling pathway
mlk04020  Calcium signaling pathway
mlk04151  PI3K-Akt signaling pathway
mlk04270  Vascular smooth muscle contraction
mlk04727  GABAergic synapse
mlk04913  Ovarian steroidogenesis
KO pathway
ko04915   
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