KEGG   PATHWAY: psiu04915
Entry
psiu04915                   Pathway                                
Name
Estrogen signaling pathway - Phocoena sinus (vaquita)
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
psiu04915  Estrogen signaling pathway
psiu04915

Other DBs
GO: 0030520
Organism
Phocoena sinus (vaquita) [GN:psiu]
Gene
116763684  ESR1; estrogen receptor [KO:K08550]
116748380  ESR2; estrogen receptor beta isoform X1 [KO:K08551]
116761650  HSP90AB1; heat shock protein HSP 90-beta isoform X1 [KO:K04079]
116749262  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
116750427  LOW QUALITY PROTEIN: heat shock protein HSP 90-beta-like [KO:K04079]
116760340  HSP90B1; LOW QUALITY PROTEIN: endoplasmin [KO:K09487]
116761047  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
116755062  LOW QUALITY PROTEIN: peptidyl-prolyl cis-trans isomerase FKBP4-like [KO:K09571] [EC:5.2.1.8]
116762634  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
116748015  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
116748530  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
116762072  HSPA1L; heat shock 70 kDa protein 1-like [KO:K03283]
116762073  HSPA1B; heat shock 70 kDa protein 1B [KO:K03283]
116762074  heat shock 70 kDa protein 1B [KO:K03283]
116756610  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
116757444  HSPA8; heat shock cognate 71 kDa protein isoform X1 [KO:K03283]
116758770  HSPA6; LOW QUALITY PROTEIN: heat shock 70 kDa protein 6 [KO:K03283]
116764262  NCOA1; LOW QUALITY PROTEIN: nuclear receptor coactivator 1 [KO:K09101] [EC:2.3.1.48]
116742161  NCOA2; nuclear receptor coactivator 2 isoform X1 [KO:K11255]
116739826  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
116738931  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
116764517  receptor-binding cancer antigen expressed on SiSo cells-like [KO:K22455]
116742619  EBAG9; receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
116745640  KRT24; LOW QUALITY PROTEIN: keratin, type I cytoskeletal 24 [KO:K07604]
116745644  keratin, type I cytoskeletal 14-like [KO:K07604]
116745645  keratin, type I cytoskeletal 17-like isoform X1 [KO:K07604]
116745647  keratin, type I cytoskeletal 19 [KO:K07604]
116745648  keratin, type I cytoskeletal 15 [KO:K07604]
116745650  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 42-like [KO:K07604]
116746186  LOW QUALITY PROTEIN: keratin, type I cuticular Ha2-like [KO:K07604]
116760306  KRT18; keratin, type I cytoskeletal 18 isoform X1 [KO:K07604]
116745233  keratin, type I cytoskeletal 12-like isoform X1 [KO:K07604]
116745234  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
116745236  keratin, type I cuticular Ha1-like [KO:K07604]
116745237  KRT35; LOW QUALITY PROTEIN: keratin, type I cuticular Ha5 [KO:K07604]
116745566  keratin, type I cytoskeletal 13-like [KO:K07604]
116758017  CTSD; cathepsin D isoform X1 [KO:K01379] [EC:3.4.23.5]
116764713  GREB1; LOW QUALITY PROTEIN: protein GREB1 [KO:K27477]
116753082  TFF1; trefoil factor 1 [KO:K22456]
116758523  PGR; progesterone receptor isoform X1 [KO:K08556]
116764662  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
116744993  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
116749519  FOS; proto-oncogene c-Fos [KO:K04379]
116761115  JUN; transcription factor AP-1 [KO:K04448]
116760263  SP1; transcription factor Sp1 [KO:K04684]
116740578  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
116740990  neuroendocrine secretory protein 55-like [KO:K04632]
116740988  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
116740153  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
116743436  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
116740660  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
116751582  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
116759445  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
116752275  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
116764233  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
116749116  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
116753224  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
116760787  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
116744731  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
116742406  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
116740403  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
116754197  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
116751566  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
116756730  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
116756632  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
116761029  ATF4; cyclic AMP-dependent transcription factor ATF-4 isoform X1 [KO:K04374]
116755320  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
116740243  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
116758621  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
116751955  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
116759300  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
116759616  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
116762930  ATF6B; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
116759758  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
116740554  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
116751918  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
116755660  SHC3; SHC-transforming protein 3 [KO:K17448]
116749591  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
116746378  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
116747062  SOS2; son of sevenless homolog 2 [KO:K03099]
116764289  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
116757893  HRAS; GTPase HRas isoform X1 [KO:K02833]
116751649  uncharacterized protein LOC116751649 [KO:K02833]
116760326  KRAS; GTPase KRas isoform X1 [KO:K07827]
116739088  NRAS; GTPase NRas [KO:K07828]
116761625  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
116747589  MAP2K1; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
116751189  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116738910  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116740620  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
116752953  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116752990  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
116751286  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116750604  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
116742613  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
116751944  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
116743673  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116759669  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116748950  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116755193  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
116762593  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
116761812  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
116749946  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
116759318  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
116744142  guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
116756285  KCNJ3; G protein-activated inward rectifier potassium channel 1 [KO:K04997]
116752719  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
116761814  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
116758063  KCNJ5; G protein-activated inward rectifier potassium channel 4 isoform X1 [KO:K04999]
116764385  POMC; pro-opiomelanocortin [KO:K05228]
116763263  OPRM1; mu-type opioid receptor isoform X1 [KO:K04215]
116762083  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
116755414  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
116749106  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
116740640  PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
116740954  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
116758215  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
116761601  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
116760890  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
116761675  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
116744236  CALM3; calmodulin-3 [KO:K02183]
116748386  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
116748713  CALM1; calmodulin-1 isoform X1 [KO:K02183]
116762110  calmodulin-1-like [KO:K02183]
116749119  calmodulin-like [KO:K02183]
116749952  calmodulin-like protein 3 [KO:K02183]
116764310  CALM2; calmodulin-2 [KO:K02183]
116759107  NOS3; LOW QUALITY PROTEIN: nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
116763496  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
psiu04010  MAPK signaling pathway
psiu04020  Calcium signaling pathway
psiu04151  PI3K-Akt signaling pathway
psiu04270  Vascular smooth muscle contraction
psiu04727  GABAergic synapse
psiu04913  Ovarian steroidogenesis
KO pathway
ko04915   
LinkDB

DBGET integrated database retrieval system