KEGG   PATHWAY: mcc04915
Entry
mcc04915                    Pathway                                
Name
Estrogen signaling pathway - Macaca mulatta (rhesus monkey)
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
mcc04915  Estrogen signaling pathway
mcc04915

Other DBs
GO: 0030520
Organism
Macaca mulatta (rhesus monkey) [GN:mcc]
Gene
100423966  TFF1; trefoil factor 1 [KO:K22456]
100424899  [KO:K04632]
100425804  [KO:K07604]
100426180  KRT14; keratin, type I cytoskeletal 14 [KO:K07604]
100426330  KRT17; keratin, type I cytoskeletal 17 [KO:K07604]
100430195  KRT27; keratin, type I cytoskeletal 27 [KO:K07604]
106994041  KRT15; keratin, type I cytoskeletal 15 [KO:K07604]
106994042  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
114669856  [KO:K03283]
114674171  [KO:K07604]
574110  ESR2; estrogen receptor beta [KO:K08551]
574141  OPRM1; mu-type opioid receptor [KO:K04215]
574275  SHC3; SHC-transforming protein 3 [KO:K17448]
574394  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
613024  PGR; progesterone receptor isoform 1 [KO:K08556]
613025  ESR1; estrogen receptor isoform X1 [KO:K08550]
613027  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
613031  TGFA; protransforming growth factor alpha isoform X2 [KO:K08774]
693455  NCOA2; nuclear receptor coactivator 2 isoform X2 [KO:K11255]
693523  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
693675  KCNJ6; G protein-activated inward rectifier potassium channel 2 isoform X1 [KO:K05000]
693753  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
694289  [KO:K04632]
694430  POMC; pro-opiomelanocortin [KO:K05228]
694656  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
694725  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
694730  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
695328  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
695559  HBEGF; proheparin-binding EGF-like growth factor precursor [KO:K08523]
695792  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
696350  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
696473  KCNJ3; G protein-activated inward rectifier potassium channel 1 [KO:K04997]
696625  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
697230  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
697434  GREB1; protein GREB1 isoform X1 [KO:K27477]
697718  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
697747  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
698478  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
698552  CALM1; calmodulin-1 isoform X1 [KO:K02183]
698569  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
698736  GRM1; metabotropic glutamate receptor 1 precursor [KO:K04603]
698830  HRAS; GTPase HRas [KO:K02833]
698996  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
699072  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
699305  EBAG9; receptor-binding cancer antigen expressed on SiSo cells isoform X2 [KO:K22455]
699310  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
699568  HSP90B1; endoplasmin precursor [KO:K09487]
700206  RARA; retinoic acid receptor alpha isoform X2 [KO:K08527]
700569  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
700591  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
700652  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
701057  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
701667  [KO:K07604]
701915  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
701951  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
702040  KRT26; keratin, type I cytoskeletal 26 [KO:K07604]
702041  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
702077  FOS; proto-oncogene c-Fos [KO:K04379]
702153  KRT10; keratin, type I cytoskeletal 10 [KO:K07604]
702274  KRT28; keratin, type I cytoskeletal 28 [KO:K07604]
702293  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
702476  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
702602  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
702710  SP1; transcription factor Sp1 [KO:K04684]
702724  KRT23; keratin, type I cytoskeletal 23 [KO:K07604]
702838  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
702950  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
703514  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
703534  CTSD; cathepsin D precursor [KO:K01379] [EC:3.4.23.5]
703669  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
703780  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
703932  KRT9; keratin, type I cytoskeletal 9 [KO:K07604]
703965  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
705431  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
705601  SOS2; son of sevenless homolog 2 [KO:K03099]
705680  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
705800  KRT33A; keratin, type I cuticular Ha3-I [KO:K07604]
705939  [KO:K07604]
706063  KRT34; keratin, type I cuticular Ha4 [KO:K07604]
706173  [KO:K07604]
706274  KRT37; keratin, type I cuticular Ha7 [KO:K07604]
706351  [KO:K02183]
706390  [KO:K07604]
706509  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
706724  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
706789  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
706830  KRT13; keratin, type I cytoskeletal 13 [KO:K07604]
707129  [KO:K07604]
707236  KRT16; keratin, type I cytoskeletal 16 [KO:K07604]
707310  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
707407  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
707977  KRAS; GTPase KRas [KO:K07827]
707978  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
707989  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
708084  MMP9; matrix metalloproteinase-9 precursor [KO:K01403] [EC:3.4.24.35]
708431  HSP90AA1; heat shock protein 90kDa alpha (cytosolic), class A member 1 [KO:K04079]
708481  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
708714  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
708717  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
708938  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
708940  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
708987  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 precursor [KO:K04615]
709089  NRAS; GTPase NRas [KO:K07828]
709412  [KO:K03283]
709728  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
709959  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
710415  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
710552  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
712159  CALML5; calmodulin-like protein 5 [KO:K02183]
713391  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
713777  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
714231  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
714611  SHC4; SHC-transforming protein 4 [KO:K17449]
714684  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
714717  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
714799  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
714981  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
715270  CALM2; calmodulin-2 [KO:K02183]
715897  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
715951  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
716098  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
716452  JUN; transcription factor AP-1 [KO:K04448]
716584  CALM3; calmodulin-3 isoform X1 [KO:K02183]
716633  [KO:K03283]
717050  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
717248  [KO:K07604]
717686  [KO:K02183]
717764  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
718019  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
718040  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
718387  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
718418  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
718524  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
718632  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
718957  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
718982  SHC1; SHC-transforming protein 1 [KO:K06279]
719367  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
719597  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
720001  HSPA6; LOW QUALITY PROTEIN: heat shock 70 kDa protein 6 [KO:K03283]
720054  HSPA1A; heat shock 70 kDa protein 1A [KO:K03283]
721021  SHC2; SHC-transforming protein 2 [KO:K17447]
721821  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
721825  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
722513  CALML3; calmodulin-like protein 3 [KO:K02183]
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
mcc04010  MAPK signaling pathway
mcc04020  Calcium signaling pathway
mcc04151  PI3K-Akt signaling pathway
mcc04270  Vascular smooth muscle contraction
mcc04727  GABAergic synapse
mcc04913  Ovarian steroidogenesis
KO pathway
ko04915   

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