KEGG   PATHWAY: afz04915
Entry
afz04915                    Pathway                                
Name
Estrogen signaling pathway - Antechinus flavipes (yellow-footed antechinus)
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
afz04915  Estrogen signaling pathway
afz04915

Other DBs
GO: 0030520
Organism
Antechinus flavipes (yellow-footed antechinus) [GN:afz]
Gene
127562338  estrogen receptor isoform X1 [KO:K08550]
127549615  estrogen receptor beta isoform X1 [KO:K08551]
127549897  LOW QUALITY PROTEIN: heat shock protein HSP 90-alpha [KO:K04079]
127561796  heat shock protein HSP 90-beta [KO:K04079]
127537901  endoplasmin [KO:K09487]
127564074  peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
127544297  peptidyl-prolyl cis-trans isomerase FKBP5-like [KO:K09571] [EC:5.2.1.8]
127561205  peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
127563001  heat shock 70 kDa protein 6-like [KO:K03283]
127563002  heat shock 70 kDa protein 6-like [KO:K03283]
127563003  heat shock 70 kDa protein 6 [KO:K03283]
127554403  heat shock cognate 71 kDa protein [KO:K03283]
127561079  heat shock 70 kDa protein 1 [KO:K03283]
127561080  heat shock 70 kDa protein 1-like [KO:K03283]
127548785  nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
127543783  nuclear receptor coactivator 2 isoform X1 [KO:K11255]
127548884  nuclear receptor coactivator 3 [KO:K11256] [EC:2.3.1.48]
127543678  apoptosis regulator Bcl-2 [KO:K02161]
127544374  receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
127564046  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 18 [KO:K07604]
127558787  keratin, type I cytoskeletal 9 [KO:K07604]
127558802  keratin, type I cytoskeletal 40 [KO:K07604]
127558803  keratin, type I cuticular Ha4-like [KO:K07604]
127558811  keratin, type I cytoskeletal 24-like [KO:K07604]
127560150  keratin, type I cytoskeletal 14 isoform X1 [KO:K07604]
127560151  keratin, type I cytoskeletal 42 [KO:K07604]
127560152  keratin, type I cytoskeletal 17 [KO:K07604]
127560153  keratin, type I cytoskeletal 15-like [KO:K07604]
127560154  keratin, type I cytoskeletal 19 [KO:K07604]
127560155  keratin, type I cytoskeletal 13 [KO:K07604]
127560156  keratin, type I cuticular Ha6 isoform X1 [KO:K07604]
127560158  keratin, type I cuticular Ha5 [KO:K07604]
127560159  LOW QUALITY PROTEIN: keratin, type I cuticular Ha2 [KO:K07604]
127560160  keratin, type I cuticular Ha8-like [KO:K07604]
127560161  keratin, type I cuticular Ha1 [KO:K07604]
127560162  keratin, type I cuticular Ha3-I-like [KO:K07604]
127560163  keratin, type I cuticular Ha1-like [KO:K07604]
127560164  keratin, type I cuticular Ha4-like [KO:K07604]
127560173  keratin, type I cytoskeletal 23 [KO:K07604]
127560174  keratin, type I cytoskeletal 20 [KO:K07604]
127560175  keratin, type I cytoskeletal 10 isoform X1 [KO:K07604]
127560177  keratin, type I cytoskeletal 28-like [KO:K07604]
127560178  keratin, type I cytoskeletal 27 [KO:K07604]
127560179  keratin, type I cytoskeletal 25 [KO:K07604]
127560180  keratin, type I cytoskeletal 26 [KO:K07604]
127560181  keratin, type I cytoskeletal 24-like [KO:K07604]
127561344  keratin, type I cuticular Ha1-like [KO:K07604]
127561352  keratin, type I cytoskeletal 12 [KO:K07604]
127561353  keratin, type I cytoskeletal 24-like [KO:K07604]
127541930  cathepsin D [KO:K01379] [EC:3.4.23.5]
127548208  protein GREB1 [KO:K27477]
127553806  trefoil factor 1 [KO:K22456]
127554912  progesterone receptor isoform X1 [KO:K08556]
127560190  retinoic acid receptor alpha isoform X1 [KO:K08527]
127549484  protein c-Fos [KO:K04379]
127563247  transcription factor Jun [KO:K04448]
127539187  LOW QUALITY PROTEIN: transcription factor Sp1 [KO:K04684]
127564070  G-protein coupled estrogen receptor 1 [KO:K04246]
127548965  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
127550415  proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
127550719  72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
127550774  matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
127549994  proheparin-binding EGF-like growth factor [KO:K08523]
127544134  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
127543614  adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
127548786  adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
127551100  adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
127554148  adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
127564773  adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
127550695  adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
127544457  adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
127542142  adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
127548938  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
127563015  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
127543087  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
127544835  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
127553178  cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
127554549  cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
127538329  LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
127538146  cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
127544947  cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
127559872  cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
127539809  cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
127540403  cyclic AMP-responsive element-binding protein 3 [KO:K09048]
127539046  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
127561098  cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
127553324  epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
127559844  SHC-transforming protein 1 isoform X1 [KO:K06279]
127545256  SHC-transforming protein 2 isoform X1 [KO:K17447]
127562429  SHC-transforming protein 3 isoform X1 [KO:K17448]
127551137  SHC-transforming protein 4 [KO:K17449]
127560474  growth factor receptor-bound protein 2 [KO:K04364]
127549759  son of sevenless homolog 2 isoform X1 [KO:K03099]
127547998  son of sevenless homolog 1 isoform X1 [KO:K03099]
127540068  GTPase HRas [KO:K02833]
127564364  ras-like protein [KO:K07827]
127564665  ras-like protein [KO:K07827]
127564806  GTPase KRas isoform X1 [KO:K07827]
127564858  GTPase KRas-like [KO:K07827]
127564890  ras-like protein [KO:K07827]
127564892  GTPase NRas-like [KO:K07827]
127541495  ras-like protein [KO:K07827]
127537819  GTPase NRas-like [KO:K07827]
127537860  GTPase NRas-like [KO:K07827]
127538037  ras-like protein [KO:K07827]
127538119  ras-like protein [KO:K07827]
127538128  LOW QUALITY PROTEIN: ras-like protein [KO:K07827]
127538787  ras-like protein [KO:K07827]
127538953  ras-like protein [KO:K07827]
127539191  ras-like protein [KO:K07827]
127539349  GTPase NRas-like [KO:K07827]
127539435  ras-like protein [KO:K07827]
127539441  ras protein let-60-like [KO:K07827]
127541494  ras-like protein [KO:K07828]
127559280  GTPase NRas [KO:K07828]
127538788  GTPase NRas-like [KO:K07828]
127538790  GTPase NRas-like [KO:K07828]
127538791  GTPase NRas-like [KO:K07828]
127538792  GTPase NRas-like [KO:K07828]
127538794  GTPase NRas-like [KO:K07828]
127552087  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
127551242  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
127544950  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
127556083  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
127545795  mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
127555896  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
127552891  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
127554245  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
127563398  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
127558297  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
127545225  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
127549861  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
127556193  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
127559596  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
127562690  gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
127561011  gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
127538251  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
127559382  guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
127554531  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
127550729  guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
127554650  G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
127553837  G protein-activated inward rectifier potassium channel 2 [KO:K05000]
127559708  G protein-activated inward rectifier potassium channel 3 [KO:K05002]
127554813  G protein-activated inward rectifier potassium channel 4 isoform X1 [KO:K04999]
127562349  mu-type opioid receptor isoform X1 [KO:K04215]
127553769  protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
127541331  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
127549225  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
127539641  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
127548499  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
127548500  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
127551451  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
127539174  inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
127561144  inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
127564795  calmodulin-A-like [KO:K02183]
127549410  calmodulin-1 [KO:K02183]
127555994  calmodulin-like protein 6 [KO:K02183]
127556283  calmodulin-3 [KO:K02183]
127551228  calmodulin-like protein 4 isoform X1 [KO:K02183]
127548058  calmodulin-2 [KO:K02183]
127564122  LOW QUALITY PROTEIN: nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
127562301  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
afz04010  MAPK signaling pathway
afz04020  Calcium signaling pathway
afz04151  PI3K-Akt signaling pathway
afz04270  Vascular smooth muscle contraction
afz04727  GABAergic synapse
afz04913  Ovarian steroidogenesis
KO pathway
ko04915   
LinkDB

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