KEGG   PATHWAY: hmh04915
Entry
hmh04915                    Pathway                                
Name
Estrogen signaling pathway - Hylobates moloch (silvery gibbon)
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
hmh04915  Estrogen signaling pathway
hmh04915

Other DBs
GO: 0030520
Organism
Hylobates moloch (silvery gibbon) [GN:hmh]
Gene
116463161  estrogen receptor [KO:K08550]
116463211  estrogen receptor isoform X1 [KO:K08550]
116484828  ESR2; estrogen receptor beta isoform X1 [KO:K08551]
116485178  HSP90AA1; heat shock protein HSP 90-alpha isoform X1 [KO:K04079]
116460213  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
116478026  HSP90B1; endoplasmin [KO:K09487]
116469780  LOW QUALITY PROTEIN: endoplasmin-like [KO:K09487]
116459633  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
116472529  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 isoform X1 [KO:K09571] [EC:5.2.1.8]
116477090  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
116460285  HSPA1B; heat shock 70 kDa protein 1B [KO:K03283]
116460286  HSPA1A; heat shock 70 kDa protein 1A [KO:K03283]
116460287  HSPA1L; heat shock 70 kDa protein 1-like [KO:K03283]
116473328  HSPA6; heat shock 70 kDa protein 6 [KO:K03283]
116480404  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
116813203  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
116461322  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
116468493  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
116478140  LOW QUALITY PROTEIN: receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
116813527  EBAG9; receptor-binding cancer antigen expressed on SiSo cells isoform X2 [KO:K22455]
116457609  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 18-like [KO:K07604]
116465556  keratin, type I cytoskeletal 18-like [KO:K07604]
116811146  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 18-like [KO:K07604]
116481026  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
116465445  keratin, type I cytoskeletal 17-like isoform X1 [KO:K07604]
116474146  keratin, type I cytoskeletal 24 [KO:K07604]
116477269  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 18-like [KO:K07604]
116474792  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
116474794  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
116474795  KRT28; keratin, type I cytoskeletal 28 [KO:K07604]
116474796  KRT27; keratin, type I cytoskeletal 27 isoform X1 [KO:K07604]
116474797  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
116474798  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
116474799  KRT23; keratin, type I cytoskeletal 23 isoform X1 [KO:K07604]
116474800  KRT26; keratin, type I cytoskeletal 26 [KO:K07604]
116474811  KRT10; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 10 [KO:K07604]
116474812  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
116474815  keratin, type I cuticular Ha3-I [KO:K07604]
116474816  keratin, type I cuticular Ha3-II isoform X1 [KO:K07604]
116474817  keratin, type I cuticular Ha8 [KO:K07604]
116474818  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
116474819  keratin, type I cuticular Ha7 [KO:K07604]
116474822  keratin, type I cuticular Ha1 isoform X1 [KO:K07604]
116474823  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
116474824  keratin, type I cuticular Ha7-like [KO:K07604]
116474825  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
116474826  KRT13; keratin, type I cytoskeletal 13 isoform X1 [KO:K07604]
116474828  KRT15; keratin, type I cytoskeletal 15 isoform X1 [KO:K07604]
116474829  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
116474830  KRT9; keratin, type I cytoskeletal 9 [KO:K07604]
116474831  KRT14; keratin, type I cytoskeletal 14 [KO:K07604]
116474832  KRT16; keratin, type I cytoskeletal 16 [KO:K07604]
116474833  KRT17; keratin, type I cytoskeletal 17 [KO:K07604]
116483633  keratin, type I cytoskeletal 17-like [KO:K07604]
116475364  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 42-like [KO:K07604]
116469160  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
116480247  GREB1; protein GREB1 isoform X2 [KO:K27477]
116482059  TFF1; trefoil factor 1 [KO:K22456]
116477412  PGR; progesterone receptor isoform X1 [KO:K08556]
116483502  TGFA; protransforming growth factor alpha [KO:K08774]
116474780  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
116456218  FOS; protein c-Fos [KO:K04379]
116457363  JUN; transcription factor Jun [KO:K04448]
116481003  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
116462909  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
116812065  guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
116463273  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
116463274  neuroendocrine secretory protein 55 [KO:K04632]
116463360  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
116463361  neuroendocrine secretory protein 55 [KO:K04632]
116461023  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
116471259  MMP2; 72 kDa type IV collagenase isoform X1 [KO:K01398] [EC:3.4.24.24]
116461334  MMP9; matrix metalloproteinase-9 isoform X2 [KO:K01403] [EC:3.4.24.35]
116471588  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
116812469  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
116457100  ADCY2; LOW QUALITY PROTEIN: adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
116480405  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
116484980  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
116466852  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
116461805  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
116471246  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
116813595  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
116462297  ADCY9; adenylate cyclase type 9 isoform X2 [KO:K08049] [EC:4.6.1.1]
116458418  PRKACG; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
116469844  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
116478588  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
116810385  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X3 [KO:K05870]
116810639  ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
116458613  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
116810327  LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
116476303  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
116469376  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
116814406  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
116483538  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
116475074  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
116812715  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X5 [KO:K09047]
116460313  cyclic AMP-dependent transcription factor ATF-6 beta-like [KO:K09049]
116812436  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
116469345  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
116464630  SHC-transforming protein 2-like [KO:K17447]
116475219  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
116481523  SHC4; SHC-transforming protein 4 [KO:K17449]
116484153  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
116484062  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
116484470  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
116466571  HRAS; GTPase HRas isoform X3 [KO:K02833]
116472788  KRAS; GTPase KRas isoform X1 [KO:K07827]
116469568  NRAS; GTPase NRas [KO:K07828]
116466754  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
116482295  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
116814342  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
116483548  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116459126  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116470222  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
116462105  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116812889  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116481263  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116478691  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
116462749  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
116473104  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
116457903  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116485139  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116480683  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116460519  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
116475316  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 isoform X1 [KO:K04615]
116469652  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
116464223  guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
116464225  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
116814165  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
116471265  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
116810787  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X2 [KO:K04997]
116481525  KCNJ6; G protein-activated inward rectifier potassium channel 2 isoform X1 [KO:K05000]
116469217  KCNJ9; G protein-activated inward rectifier potassium channel 3 isoform X2 [KO:K05002]
116477486  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
116480413  POMC; pro-opiomelanocortin [KO:K05228]
116473184  OPRM1; mu-type opioid receptor isoform X1 [KO:K04215]
116473376  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
116475178  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
116468938  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
116461202  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
116461370  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858] [EC:3.1.4.11]
116481969  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X6 [KO:K05858] [EC:3.1.4.11]
116466681  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
116472793  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
116459671  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
116467516  uncharacterized protein LOC116467516 [KO:K02183]
116485193  CALM1; calmodulin-1 isoform X2 [KO:K02183]
116478308  CALM3; calmodulin-3 [KO:K02183]
116482339  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
116813883  CALML6; calmodulin-like protein 6 [KO:K02183]
116483146  CALM2; calmodulin-2 isoform X1 [KO:K02183]
116466871  calmodulin-1-like [KO:K02183]
116474613  CALML5; calmodulin-like protein 5 [KO:K02183]
116474621  CALML3; calmodulin-like protein 3 [KO:K02183]
116814534  NOS3; nitric oxide synthase 3 isoform X1 [KO:K13242] [EC:1.14.13.39]
116463111  metabotropic glutamate receptor 1-like isoform X1 [KO:K04603]
116463144  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
hmh04010  MAPK signaling pathway
hmh04020  Calcium signaling pathway
hmh04151  PI3K-Akt signaling pathway
hmh04270  Vascular smooth muscle contraction
hmh04727  GABAergic synapse
hmh04913  Ovarian steroidogenesis
KO pathway
ko04915   
LinkDB

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