KEGG   PATHWAY: lruf04915
Entry
lruf04915                   Pathway                                
Name
Estrogen signaling pathway - Lynx rufus (bobcat)
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
lruf04915  Estrogen signaling pathway
lruf04915

Other DBs
GO: 0030520
Organism
Lynx rufus (bobcat) [GN:lruf]
Gene
124529259  estrogen receptor [KO:K08550]
124512326  estrogen receptor beta isoform X1 [KO:K08551]
124512510  heat shock protein HSP 90-alpha [KO:K04079]
124528527  heat shock protein HSP 90-beta [KO:K04079]
124501451  endoplasmin [KO:K09487]
124528548  peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
124502032  peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
124505172  heat shock cognate 71 kDa protein [KO:K03283]
124526648  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
124520272  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
124527622  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
124528066  heat shock 70 kDa protein 1 [KO:K03283]
124528067  heat shock 70 kDa protein 1 [KO:K03283]
124528068  heat shock 70 kDa protein 1-like [KO:K03283]
124503065  nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
124507704  nuclear receptor coactivator 2 isoform X1 [KO:K11255]
124503159  nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
124517105  apoptosis regulator Bcl-2 [KO:K02161]
124507763  receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
124512791  keratin, type I cytoskeletal 20-like [KO:K07604]
124512889  keratin, type I cytoskeletal 10-like isoform X1 [KO:K07604]
124512917  keratin, type I cytoskeletal 27 [KO:K07604]
124512920  keratin, type I cytoskeletal 25 [KO:K07604]
124512927  keratin, type I cytoskeletal 28 [KO:K07604]
124512932  keratin, type I cytoskeletal 26-like [KO:K07604]
124512933  keratin, type I cytoskeletal 24-like isoform X1 [KO:K07604]
124512974  keratin, type I cytoskeletal 40-like [KO:K07604]
124513140  keratin, type I cytoskeletal 39-like [KO:K07604]
124513350  keratin, type I cytoskeletal 23-like isoform X1 [KO:K07604]
124513600  keratin, type I cytoskeletal 12-like [KO:K07604]
124501460  keratin, type I cytoskeletal 18 [KO:K07604]
124522137  keratin, type I cuticular Ha6 [KO:K07604]
124522138  keratin, type I cuticular Ha5 [KO:K07604]
124522139  keratin, type I cuticular Ha1 [KO:K07604]
124522144  keratin, type I cuticular Ha8-like [KO:K07604]
124522145  keratin, type I cuticular Ha2-like [KO:K07604]
124522146  keratin, type I cuticular Ha8-like [KO:K07604]
124522147  keratin, type I cuticular Ha8-like [KO:K07604]
124522148  keratin, type I cuticular Ha3-II [KO:K07604]
124522149  keratin, type I cuticular Ha4 [KO:K07604]
124522158  keratin, type I cuticular Ha3-I [KO:K07604]
124522159  keratin, type I cytoskeletal 14-like [KO:K07604]
124522160  keratin, type I cytoskeletal 42-like [KO:K07604]
124522161  keratin, type I cytoskeletal 13 [KO:K07604]
124522162  keratin, type I cytoskeletal 16 [KO:K07604]
124522165  keratin, type I cytoskeletal 17 [KO:K07604]
124522166  keratin, type I cytoskeletal 15 [KO:K07604]
124522201  keratin, type I cytoskeletal 19 [KO:K07604]
124522218  keratin, type I cytoskeletal 9-like [KO:K07604]
124527879  cathepsin D [KO:K01379] [EC:3.4.23.5]
124504346  protein GREB1 [KO:K27477]
124525977  trefoil factor 1-like [KO:K22456]
124505524  progesterone receptor-like isoform X1 [KO:K08556]
124503927  protransforming growth factor alpha [KO:K08774]
124513342  LOW QUALITY PROTEIN: retinoic acid receptor alpha-like [KO:K08527]
124512631  protein c-Fos [KO:K04379]
124516273  transcription factor Jun [KO:K04448]
124502539  transcription factor Sp1 isoform X1 [KO:K04684]
124519124  G-protein coupled estrogen receptor 1 [KO:K04246]
124503012  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
124503255  neuroendocrine secretory protein 55 [KO:K04632]
124504000  proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
124511320  72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
124503402  matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
124526024  proheparin-binding EGF-like growth factor [KO:K08523]
124524637  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
124508049  adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
124503617  adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
124508863  adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
124526579  adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
124501854  adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
124511307  adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
124507481  adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
124517827  adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
124514583  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
124524048  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
124516566  cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
124514138  cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
124502100  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
124524408  cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
124506275  cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
124521809  cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
124501745  cyclic AMP-responsive element-binding protein 3-like isoform X1 [KO:K09048]
124523866  cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
124524308  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
124528650  cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
124523868  epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
124521760  SHC-transforming protein 1 isoform X1 [KO:K06279]
124527699  SHC-transforming protein 2 isoform X1 [KO:K17447]
124524856  SHC-transforming protein 3 [KO:K17448]
124508608  SHC-transforming protein 4 [KO:K17449]
124513422  growth factor receptor-bound protein 2 [KO:K04364]
124504040  son of sevenless homolog 1 isoform X1 [KO:K03099]
124512209  son of sevenless homolog 2 isoform X1 [KO:K03099]
124527565  GTPase HRas isoform X1 [KO:K02833]
124502703  GTPase KRas isoform X1 [KO:K07827]
124516245  GTPase NRas [KO:K07828]
124523760  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
124508471  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
124524782  dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
124517731  mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
124519861  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
124525968  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
124527077  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
124514827  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
124517840  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
124514527  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
124523730  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
124510270  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
124511119  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124512474  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124528989  gamma-aminobutyric acid type B receptor subunit 1 [KO:K04615]
124502272  gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
124514443  guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
124523010  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
124524167  guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
124511323  guanine nucleotide-binding protein G(o) subunit alpha-like [KO:K04534]
124516578  G protein-activated inward rectifier potassium channel 1 [KO:K04997]
124527316  G protein-activated inward rectifier potassium channel 2 [KO:K05000]
124521864  G protein-activated inward rectifier potassium channel 3 [KO:K05002]
124505372  G protein-activated inward rectifier potassium channel 4 [KO:K04999]
124504250  pro-opiomelanocortin [KO:K05228]
124528129  mu-type opioid receptor isoform X1 [KO:K04215]
124523091  protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
124528694  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
124503791  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4-like [KO:K05858] [EC:3.1.4.11]
124503878  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
124505119  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
124508712  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
124522957  inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
124501326  inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
124528059  inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
124503379  calmodulin-1 [KO:K02183]
124510996  calmodulin-1 [KO:K02183]
124512578  calmodulin-1 [KO:K02183]
124514424  LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
124508455  LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
124502502  calmodulin-like protein 3 [KO:K02183]
124502628  calmodulin-like [KO:K02183]
124524465  nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
124528740  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
lruf04010  MAPK signaling pathway
lruf04020  Calcium signaling pathway
lruf04151  PI3K-Akt signaling pathway
lruf04270  Vascular smooth muscle contraction
lruf04727  GABAergic synapse
lruf04913  Ovarian steroidogenesis
KO pathway
ko04915   
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