KEGG   PATHWAY: pcoo04915
Entry
pcoo04915                   Pathway                                
Name
Estrogen signaling pathway - Puma concolor (puma)
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
pcoo04915  Estrogen signaling pathway
pcoo04915

Other DBs
GO: 0030520
Organism
Puma concolor (puma) [GN:pcoo]
Gene
112862113  ESR1; estrogen receptor isoform X1 [KO:K08550]
112855128  ESR2; estrogen receptor beta [KO:K08551]
112855434  HSP90AA1; heat shock protein HSP 90-alpha isoform X1 [KO:K04079]
112862791  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
112863931  HSP90B1; endoplasmin [KO:K09487]
112862083  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
112867352  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
112865282  HSPA8; LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein [KO:K03283]
112853784  heat shock 70 kDa protein 1-like [KO:K03283]
112853785  heat shock 70 kDa protein 1-like [KO:K03283]
112864088  NCOA1; nuclear receptor coactivator 1 [KO:K09101] [EC:2.3.1.48]
112859515  NCOA2; nuclear receptor coactivator 2 [KO:K11255]
112869122  NCOA3; nuclear receptor coactivator 3 [KO:K11256] [EC:2.3.1.48]
112868295  BCL2; LOW QUALITY PROTEIN: apoptosis regulator Bcl-2 [KO:K02161]
112859464  EBAG9; receptor-binding cancer antigen expressed on SiSo cells [KO:K22455]
112853955  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
112853956  keratin, type I cytoskeletal 13-like [KO:K07604]
112853958  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
112854010  keratin, type I cytoskeletal 42 [KO:K07604]
112854011  keratin, type I cytoskeletal 16-like [KO:K07604]
112854012  LOW QUALITY PROTEIN: keratin, type I cytoskeletal 19-like [KO:K07604]
112854013  keratin, type I cytoskeletal 15-like [KO:K07604]
112854014  LOW QUALITY PROTEIN: keratin, type I cuticular Ha7-like [KO:K07604]
112854015  keratin, type I microfibrillar 48 kDa, component 8C-1-like [KO:K07604]
112854018  KRT10; keratin, type I cytoskeletal 10 [KO:K07604]
112854027  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
112854057  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
112854060  keratin, type I cuticular Ha3-I [KO:K07604]
112854087  keratin, type I cytoskeletal 17 [KO:K07604]
112854123  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
112854124  keratin, type I cuticular Ha4 [KO:K07604]
112854145  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
112854155  KRT26; keratin, type I cytoskeletal 26 [KO:K07604]
112854185  KRT24; keratin, type I cytoskeletal 24 isoform X1 [KO:K07604]
112854191  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
112854205  keratin, type I cuticular Ha6 [KO:K07604]
112854207  keratin, type I cuticular Ha1 [KO:K07604]
112854210  KRT9; keratin, type I cytoskeletal 9 [KO:K07604]
112854211  keratin, type I cytoskeletal 14 [KO:K07604]
112854213  keratin, type I cytoskeletal 28 [KO:K07604]
112854214  keratin, type I cytoskeletal 27 [KO:K07604]
112867324  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
112864393  GREB1; protein GREB1 [KO:K27477]
112864893  PGR; progesterone receptor isoform X1 [KO:K08556]
112869672  TGFA; protransforming growth factor alpha [KO:K08774]
112854085  RARA; retinoic acid receptor alpha [KO:K08527]
112854981  FOS; proto-oncogene c-Fos [KO:K04379]
112872218  JUN; transcription factor AP-1 [KO:K04448]
112867279  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
112860132  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
112869078  guanine nucleotide-binding protein G(s) subunit alpha-like [KO:K04632]
112869430  neuroendocrine secretory protein 55 [KO:K04632]
112869273  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
112857297  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
112869471  MMP9; LOW QUALITY PROTEIN: matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
112860906  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
112859788  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
112860207  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
112864041  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
112855238  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
112849881  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
112867731  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
112857348  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
112859389  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
112853291  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
112852313  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
112871920  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
112848555  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
112848765  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
112863930  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
112851773  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
112852536  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
112865439  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
112871786  CREB3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3 [KO:K09048]
112866754  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
112866756  CREB5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
112853637  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
112860068  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
112851716  SHC1; SHC-transforming protein 1 [KO:K06279]
112852752  SHC2; SHC-transforming protein 2 [KO:K17447]
112868533  SHC3; SHC-transforming protein 3 [KO:K17448]
112856265  SHC4; SHC-transforming protein 4 [KO:K17449]
112864567  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
112855446  SOS2; son of sevenless homolog 2 [KO:K03099]
112864130  SOS1; son of sevenless homolog 1 [KO:K03099]
112868012  KRAS; GTPase KRas isoform X1 [KO:K07827]
112848478  NRAS; GTPase NRas [KO:K07828]
112859466  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
112855545  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
112852828  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
112856394  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
112870302  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
112849397  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
112849524  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
112848856  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
112861619  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
112868847  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
112863208  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112851313  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112852537  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
112853616  GABBR1; LOW QUALITY PROTEIN: gamma-aminobutyric acid type B receptor subunit 1 [KO:K04615]
112852602  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
112872095  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
112866857  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
112857493  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
112865957  KCNJ3; G protein-activated inward rectifier potassium channel 1 [KO:K04997]
112849482  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
112865404  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
112862076  OPRM1; mu-type opioid receptor isoform X1 [KO:K04215]
112852480  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
112868673  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
112855622  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
112869362  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
112869587  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
112851908  PLCB3; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
112858201  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
112867360  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
112862849  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
112868964  CALM2; calmodulin-2 [KO:K02183]
112856098  calmodulin-like [KO:K02183]
112856351  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
112850749  CALM3; calmodulin-3 [KO:K02183]
112867219  calmodulin-like protein 3 [KO:K02183]
112867742  calmodulin-like [KO:K02183]
112866504  NOS3; LOW QUALITY PROTEIN: nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
112862043  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
pcoo04010  MAPK signaling pathway
pcoo04020  Calcium signaling pathway
pcoo04151  PI3K-Akt signaling pathway
pcoo04270  Vascular smooth muscle contraction
pcoo04727  GABAergic synapse
pcoo04913  Ovarian steroidogenesis
KO pathway
ko04915   
LinkDB

DBGET integrated database retrieval system