KEGG   PATHWAY: mmur04915
Entry
mmur04915                   Pathway                                
Name
Estrogen signaling pathway - Microcebus murinus (gray mouse lemur)
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
mmur04915  Estrogen signaling pathway
mmur04915

Other DBs
GO: 0030520
Organism
Microcebus murinus (gray mouse lemur) [GN:mmur]
Gene
105858071  ESR1; estrogen receptor [KO:K08550]
105878331  ESR2; estrogen receptor beta isoform X1 [KO:K08551]
105859524  HSP90AB1; LOW QUALITY PROTEIN: heat shock protein HSP 90-beta [KO:K04079]
105861065  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
105875581  HSP90B1; endoplasmin [KO:K09487]
105881485  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
105861383  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
105854849  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
105885170  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
105858167  heat shock 70 kDa protein 1 [KO:K03283]
105858168  heat shock 70 kDa protein 1-like [KO:K03283]
105873559  HSPA6; heat shock 70 kDa protein 6 [KO:K03283]
105884347  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
105874694  NCOA2; nuclear receptor coactivator 2 isoform X3 [KO:K11255]
105859273  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
105876728  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
105883259  EBAG9; receptor-binding cancer antigen expressed on SiSo cells isoform X1 [KO:K22455]
105870575  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
105872032  KRT9; keratin, type I cytoskeletal 9 [KO:K07604]
105872033  keratin, type I cytoskeletal 16 isoform X1 [KO:K07604]
105872034  keratin, type I cytoskeletal 15 isoform X1 [KO:K07604]
105872035  keratin, type I cytoskeletal 14 [KO:K07604]
105872036  KRT17; keratin, type I cytoskeletal 17 [KO:K07604]
105872037  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
105872038  keratin, type I cytoskeletal 13 isoform X1 [KO:K07604]
105872039  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
105872040  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
105872041  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
105872042  keratin, type I cuticular Ha1 [KO:K07604]
105872043  LOW QUALITY PROTEIN: keratin, type I cuticular Ha4-like [KO:K07604]
105872044  keratin, type I cuticular Ha3-I [KO:K07604]
105872061  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
105872062  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
105872063  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
105872064  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
105872065  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
105872066  KRT10; keratin, type I cytoskeletal 10 [KO:K07604]
105872067  KRT28; keratin, type I cytoskeletal 28 [KO:K07604]
105872068  KRT27; keratin, type I cytoskeletal 27 [KO:K07604]
105872070  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
105872071  KRT26; keratin, type I cytoskeletal 26 [KO:K07604]
105872072  keratin, type I cytoskeletal 24-like [KO:K07604]
105872073  keratin, type I cytoskeletal 24-like [KO:K07604]
105872191  keratin, type I cuticular Ha8-like [KO:K07604]
105872193  keratin, type I cuticular Ha7-like [KO:K07604]
105872194  keratin, type I cuticular Ha3-I-like [KO:K07604]
105859823  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
105880222  GREB1; protein GREB1 isoform X1 [KO:K27477]
105874579  PGR; progesterone receptor isoform X1 [KO:K08556]
105863259  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
105872083  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
105858849  FOS; proto-oncogene c-Fos [KO:K04379]
105882585  JUN; transcription factor AP-1 [KO:K04448]
105870777  SP1; transcription factor Sp1 [KO:K04684]
105868377  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
105874518  guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632]
105874520  neuroendocrine secretory protein 55-like [KO:K04632]
105866030  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
105866549  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
105859286  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
105862636  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
105870668  ADCY1; LOW QUALITY PROTEIN: adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
105859934  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
105884349  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
105866617  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
105879870  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
105867497  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
105884745  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
105882731  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
105859653  ADCY9; adenylate cyclase type 9 isoform X2 [KO:K08049] [EC:4.6.1.1]
105867963  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
105861780  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X2 [KO:K04345] [EC:2.7.11.11]
105864304  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
105865052  ATF2; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
105858535  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105873936  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
105874305  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
105885209  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
105885942  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
105859108  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
105855129  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
105858143  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
105877217  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
105873192  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
105860825  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
105876163  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
105870730  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
105878936  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
105867678  SOS2; son of sevenless homolog 2 [KO:K03099]
105884529  SOS1; son of sevenless homolog 1 [KO:K03099]
105874032  HRAS; GTPase HRas [KO:K02833]
105857286  KRAS; GTPase KRas isoform X1 [KO:K07827]
105878710  NRAS; GTPase NRas [KO:K07828]
105882676  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105868083  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105873938  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105870697  mitogen-activated protein kinase 6-like [KO:K04371] [EC:2.7.11.24]
105877796  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105871124  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105862660  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105855821  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105886063  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105881219  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
105855026  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105877483  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
105861093  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105876768  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105863738  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105868940  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
105873786  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
105874990  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
105864008  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
105879338  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
105866545  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
105859138  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
105881285  KCNJ6; G protein-activated inward rectifier potassium channel 2 isoform X2 [KO:K05000]
105862704  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
105875338  KCNJ5; LOW QUALITY PROTEIN: G protein-activated inward rectifier potassium channel 4 [KO:K04999]
105884309  POMC; pro-opiomelanocortin [KO:K05228]
105862109  mu-type opioid receptor isoform X1 [KO:K04215]
105870100  mu-type opioid receptor-like [KO:K04215]
105875067  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
105868697  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
105861219  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
105878468  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
105872433  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
105880040  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
105869384  ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
105857276  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
105861402  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
105867016  CALM2; calmodulin [KO:K02183]
105876291  CALM1; calmodulin [KO:K02183]
105869569  CALM3; calmodulin [KO:K02183]
105870055  calmodulin-like [KO:K02183]
105877681  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
105858210  calmodulin-alpha-like [KO:K02183]
105873434  CALML4; calmodulin-like protein 4 [KO:K02183]
105883168  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
105864337  GRM1; metabotropic glutamate receptor 1 [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
mmur04010  MAPK signaling pathway
mmur04020  Calcium signaling pathway
mmur04151  PI3K-Akt signaling pathway
mmur04270  Vascular smooth muscle contraction
mmur04727  GABAergic synapse
mmur04913  Ovarian steroidogenesis
KO pathway
ko04915   
LinkDB

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