KEGG   PATHWAY: ajm04915
Entry
ajm04915                    Pathway                                
Name
Estrogen signaling pathway - Artibeus jamaicensis (Jamaican fruit-eating bat)
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
ajm04915  Estrogen signaling pathway
ajm04915

Other DBs
GO: 0030520
Organism
Artibeus jamaicensis (Jamaican fruit-eating bat) [GN:ajm]
Gene
119057914  estrogen receptor [KO:K08550]
119059984  ESR2; estrogen receptor beta [KO:K08551]
119037939  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
119041136  LOW QUALITY PROTEIN: putative heat shock protein HSP 90-beta-3 [KO:K04079]
119046156  heat shock protein 90-5, chloroplastic-like [KO:K04079]
119061428  endoplasmin homolog [KO:K04079]
119047198  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
119047665  heat shock protein 81-1 [KO:K04079]
119060253  HSP90B1; endoplasmin [KO:K09487]
119040824  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
119050073  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 isoform X1 [KO:K09571] [EC:5.2.1.8]
119044063  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
119039490  heat shock cognate 70 kDa protein 2 [KO:K03283]
119039566  heat shock 70 kDa protein 6 [KO:K03283]
119051561  stromal 70 kDa heat shock-related protein, chloroplastic-like [KO:K03283]
119059918  heat shock 70 kDa protein 7, chloroplastic-like [KO:K03283]
119046069  heat shock cognate 70 kDa protein 2-like [KO:K03283]
119053663  heat shock 70 kDa protein cognate 4 isoform X1 [KO:K03283]
119053737  heat shock 70 kDa protein 1-like [KO:K03283]
119053750  heat shock 70 kDa protein 1 [KO:K03283]
119062443  heat shock 70 kDa protein 1A [KO:K03283]
119048100  heat shock-related 70 kDa protein 2-like [KO:K03283]
119058044  heat shock cognate 70 kDa protein 2-like [KO:K03283]
119050416  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
119051976  NCOA2; nuclear receptor coactivator 2 [KO:K11255]
119063224  NCOA3; nuclear receptor coactivator 3 [KO:K11256] [EC:2.3.1.48]
119057575  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
119065036  EBAG9; receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
119043498  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
119037492  keratin, type I cytoskeletal 14 isoform X1 [KO:K07604]
119037493  KRT16; keratin, type I cytoskeletal 16 [KO:K07604]
119037494  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
119037495  KRT17; keratin, type I cytoskeletal 17 [KO:K07604]
119037511  KRT24; keratin, type I cytoskeletal 24 [KO:K07604]
119037512  keratin, type I cuticular Ha1 [KO:K07604]
119037513  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
119037515  keratin, type I cuticular Ha4-like [KO:K07604]
119037519  keratin, type I cytoskeletal 25 [KO:K07604]
119037520  keratin, type I cuticular Ha3-I-like [KO:K07604]
119037521  keratin, type I cuticular Ha3-I-like [KO:K07604]
119037522  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
119037523  KRT10; keratin, type I cytoskeletal 10 isoform X1 [KO:K07604]
119037524  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
119037526  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
119037532  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
119037533  keratin, type I cuticular Ha7-like [KO:K07604]
119037534  keratin, type I cuticular Ha7-like [KO:K07604]
119037539  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
119037540  keratin, type I cytoskeletal 28-like [KO:K07604]
119037543  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
119037561  keratin, type I cytoskeletal 26-like [KO:K07604]
119037562  keratin, type I cytoskeletal 27 [KO:K07604]
119037568  keratin, type I cytoskeletal 15 isoform X1 [KO:K07604]
119037571  keratin, type I cytoskeletal 13-like [KO:K07604]
119037576  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
119051237  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 18-like [KO:K07604]
119060030  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 18-like [KO:K07604]
119061463  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 19-like [KO:K07604]
119046391  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 18-like [KO:K07604]
119059015  lysosomal aspartic protease-like [KO:K01379] [EC:3.4.23.5]
119057540  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
119054010  GREB1; protein GREB1 isoform X1 [KO:K27477]
119048836  TFF1; trefoil factor 1 [KO:K22456]
119058017  PGR; progesterone receptor isoform X1 [KO:K08556]
119035804  TGFA; LOW QUALITY PROTEIN: protransforming growth factor alpha [KO:K08774]
119037490  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
119049259  FOS; proto-oncogene c-Fos [KO:K04379]
119051654  JUN; transcription factor AP-1 [KO:K04448]
119043517  SP1; transcription factor Sp1 [KO:K04684]
119043771  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
119055313  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
119055349  neuroendocrine secretory protein 55-like [KO:K04632]
119063248  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
119046441  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
119063184  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
119051085  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
119057313  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
119049317  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
119050413  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
119037286  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
119039523  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
119042160  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
119046468  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
119064806  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
119056281  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
119062886  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
119049690  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
119064343  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
119057201  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
119060217  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
119045974  activating transcription factor of chaperone-like [KO:K04374]
119061780  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
119048742  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
119063765  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
119064485  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
119065205  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
119035286  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
119053748  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
119057339  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
119061761  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
119044619  SHC2; SHC-transforming protein 2 [KO:K17447]
119040940  SHC3; SHC-transforming protein 3 [KO:K17448]
119057612  SHC4; SHC-transforming protein 4 [KO:K17449]
119058521  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
119052051  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
119056966  SOS2; son of sevenless homolog 2 [KO:K03099]
119062206  HRAS; GTPase HRas isoform X1 [KO:K02833]
119048987  KRAS; GTPase KRas isoform X1 [KO:K07827]
119041711  NRAS; GTPase NRas [KO:K07828]
119044815  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
119057101  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
119063754  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
119040930  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
119059157  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
119043036  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
119044861  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
119064089  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
119052227  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
119053288  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
119046830  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
119040479  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119053408  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119063115  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119045908  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
119065154  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
119036589  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
119040343  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
119054511  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha isoform X1 [KO:K04630]
119046437  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
119047907  KCNJ3; G protein-activated inward rectifier potassium channel 1 [KO:K04997]
119035740  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
119048476  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
119041031  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
119046323  G protein-activated inward rectifier potassium channel 4 [KO:K04999]
119050328  POMC; pro-opiomelanocortin [KO:K05228]
119058438  OPRM1; mu-type opioid receptor [KO:K04215]
119041430  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
119052107  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
119045446  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
119061296  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
119057282  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
119036740  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
119048995  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
119041225  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
119035940  calmodulin-2/4 [KO:K02183]
119037894  CALM1; calmodulin-1 [KO:K02183]
119053333  calmodulin-2/4 [KO:K02183]
119060885  CALM2; calmodulin-2 [KO:K02183]
119056493  calmodulin-A-like [KO:K02183]
119056633  CALM3; calmodulin-3 [KO:K02183]
119057111  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
119057312  calmodulin-alpha-like [KO:K02183]
119057735  CALML3; calmodulin-like protein 3 [KO:K02183]
119050509  CALML6; calmodulin-like protein 6 [KO:K02183]
119039263  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
119049056  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
ajm04010  MAPK signaling pathway
ajm04020  Calcium signaling pathway
ajm04151  PI3K-Akt signaling pathway
ajm04270  Vascular smooth muscle contraction
ajm04727  GABAergic synapse
ajm04913  Ovarian steroidogenesis
KO pathway
ko04915   
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