KEGG   PATHWAY: bbub04915
Entry
bbub04915                   Pathway                                
Name
Estrogen signaling pathway - Bubalus bubalis (water buffalo)
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
bbub04915  Estrogen signaling pathway
bbub04915

Other DBs
GO: 0030520
Organism
Bubalus bubalis (water buffalo) [GN:bbub]
Gene
102408657  ESR1; estrogen receptor [KO:K08550]
102390058  ESR2; estrogen receptor beta isoform X1 [KO:K08551]
102389823  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
102409833  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
102406400  LOW QUALITY PROTEIN: heat shock protein HSP 90-alpha-like [KO:K04079]
102410871  LOW QUALITY PROTEIN: heat shock protein HSP 90-beta-like [KO:K04079]
102399111  HSP90B1; endoplasmin [KO:K09487]
102389391  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
102394100  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
102411960  HSPA6; heat shock 70 kDa protein 6 [KO:K03283]
102411242  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
102408332  heat shock 70 kDa protein 1-like [KO:K03283]
102409533  heat shock 70 kDa protein 1A [KO:K03283]
102393502  heat shock cognate 71 kDa protein [KO:K03283]
102406567  NCOA1; nuclear receptor coactivator 1 isoform X2 [KO:K09101] [EC:2.3.1.48]
102389410  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
102407392  NCOA3; nuclear receptor coactivator 3 isoform X4 [KO:K11256] [EC:2.3.1.48]
102402077  BCL2; apoptosis regulator Bcl-2 isoform X3 [KO:K02161]
102412426  EBAG9; receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
102390254  KRT24; keratin, type I cytoskeletal 24 [KO:K07604]
102390593  keratin, type I cytoskeletal 25 [KO:K07604]
102390917  KRT26; keratin, type I cytoskeletal 26 [KO:K07604]
102391255  KRT27; keratin, type I cytoskeletal 27 isoform X1 [KO:K07604]
102391599  KRT10; keratin, type I cytoskeletal 10 isoform X1 [KO:K07604]
102391927  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
102392254  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
102392569  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
102398035  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 16 [KO:K07604]
102392547  keratin, type I microfibrillar 48 kDa, component 8C-1 [KO:K07604]
102394194  KRT28; keratin, type I cytoskeletal 28 isoform X2 [KO:K07604]
102416571  KRT33A; keratin, type I cuticular Ha3-I [KO:K07604]
102389131  keratin, type I microfibrillar 48 kDa, component 8C-1-like [KO:K07604]
102389471  keratin, type I microfibrillar 48 kDa, component 8C-1 [KO:K07604]
102389784  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
102390116  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
102390667  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
102390995  keratin, type I cytoskeletal 13 [KO:K07604]
102391568  KRT15; keratin, type I cytoskeletal 15 [KO:K07604]
102391899  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
102392224  KRT9; keratin, type I cytoskeletal 9 [KO:K07604]
102392881  LOW QUALITY PROTEIN: keratin, type I cuticular Ha7 [KO:K07604]
102393197  KRT38; keratin, type I cuticular Ha8 [KO:K07604]
102396299  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
102397228  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
102393862  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
102397396  keratin, type I cytoskeletal 17 [KO:K07604]
102397719  keratin, type I cytoskeletal 42 [KO:K07604]
102398359  keratin, type I cytoskeletal 14 [KO:K07604]
102408718  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 39-like [KO:K07604]
102404392  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
102400411  GREB1; protein GREB1 isoform X3 [KO:K27477]
102414405  TFF1; trefoil factor 1 [KO:K22456]
102403123  PGR; progesterone receptor isoform X2 [KO:K08556]
102406217  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
102412210  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
102393791  FOS; proto-oncogene C-Fos [KO:K04379]
102405224  JUN; transcription factor AP-1 [KO:K04448]
102392142  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
102408597  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
112577614  neuroendocrine secretory protein 55 [KO:K04632]
102410133  SRC; proto-oncogene tyrosine-protein kinase Src isoform X2 [KO:K05704] [EC:2.7.10.2]
102401701  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
102414528  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
102411668  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
102415323  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
102412622  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
102407976  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
102408103  ADCY4; adenylate cyclase type 4 isoform X2 [KO:K08044] [EC:4.6.1.1]
102405387  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
102407637  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
102410456  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
102395302  ADCY8; adenylate cyclase type 8 isoform X3 [KO:K08048] [EC:4.6.1.1]
102404282  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
102392366  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
102413383  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X4 [KO:K04345] [EC:2.7.11.11]
102401906  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
102410577  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
102393344  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
112580290  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
102406078  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
102395032  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
102400784  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
102416630  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
102398301  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X2 [KO:K09048]
102400864  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X4 [KO:K09047]
102392963  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X3 [KO:K09049]
102398103  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102409515  SHC1; SHC-transforming protein 1 isoform X4 [KO:K06279]
102389953  SHC2; SHC-transforming protein 2 isoform X2 [KO:K17447]
102411865  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
102406154  SHC4; SHC-transforming protein 4 isoform X2 [KO:K17449]
102394713  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
102412823  SOS2; son of sevenless homolog 2 [KO:K03099]
102392913  SOS1; son of sevenless homolog 1 isoform X3 [KO:K03099]
112587129  GTPase HRas-like [KO:K02833]
102392995  KRAS; GTPase KRas isoform X2 [KO:K07827]
102399487  NRAS; GTPase NRas isoform X2 [KO:K07828]
102412922  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102396842  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102401744  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
102396206  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
102403296  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102404165  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102400519  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102404610  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102415109  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102404517  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
102395384  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
102397969  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102398761  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102391021  AKT3; RAC-gamma serine/threonine-protein kinase isoform X4 [KO:K04456] [EC:2.7.11.1]
102399037  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 isoform X1 [KO:K04615]
102393080  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X3 [KO:K04615]
102413668  GNAI2; guanine nucleotide-binding protein G(I) subunit alpha-2 [KO:K04630]
102401306  GNAI1; guanine nucleotide-binding protein G(I) subunit alpha-1 [KO:K04630]
102409247  GNAI3; guanine nucleotide-binding protein G(I) subunit alpha-3 [KO:K04630]
102394976  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X2 [KO:K04534]
102410731  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
102400825  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
102402372  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
102392060  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
102410708  POMC; pro-opiomelanocortin [KO:K05228]
102390735  OPRM1; mu-type opioid receptor [KO:K04215]
102407491  PRKCD; protein kinase C delta type isoform X4 [KO:K06068] [EC:2.7.11.13]
102409250  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
102412320  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
102405830  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858] [EC:3.1.4.11]
102413748  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
102389945  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
102412452  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X8 [KO:K04958]
102401062  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X2 [KO:K04959]
102409793  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
102391725  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
102403292  calmodulin-1-like [KO:K02183]
102416387  calmodulin [KO:K02183]
102405655  calmodulin [KO:K02183]
102393421  calmodulin-1-like [KO:K02183]
102408582  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
123466194  calmodulin-1-like [KO:K02183]
102396094  CALM1; calmodulin-1 isoform X2 [KO:K02183]
102406525  CALM3; calmodulin-3 [KO:K02183]
102410813  CALM2; calmodulin-2 [KO:K02183]
102408451  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
102414394  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
bbub04010  MAPK signaling pathway
bbub04020  Calcium signaling pathway
bbub04151  PI3K-Akt signaling pathway
bbub04270  Vascular smooth muscle contraction
bbub04727  GABAergic synapse
bbub04913  Ovarian steroidogenesis
KO pathway
ko04915   
LinkDB

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