Entry
Name
Estrogen signaling pathway - Mus musculus (house mouse)
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
BRITE hierarchy
Pathway map
Ortholog table
Other DBs
Organism
Mus musculus (house mouse) [GN:
mmu ]
Gene
15519 Hsp90aa1; heat shock protein 90, alpha (cytosolic), class A member 1 [KO:K04079 ]
15516 Hsp90ab1; heat shock protein 90 alpha (cytosolic), class B member 1 [KO:K04079 ]
22027 Hsp90b1; heat shock protein 90, beta (Grp94), member 1 [KO:K09487 ]
17978 Ncoa2; nuclear receptor coactivator 2 [KO:K11255 ]
55960 Ebag9; estrogen receptor-binding fragment-associated gene 9 [KO:K22455 ]
268527 Greb1; gene regulated by estrogen in breast cancer protein [KO:K27477 ]
21802 Tgfa; transforming growth factor alpha [KO:K08774 ]
20683 Sp1; trans-acting transcription factor 1 [KO:K04684 ]
76854 Gper1; G protein-coupled estrogen receptor 1 [KO:K04246 ]
15200 Hbegf; heparin-binding EGF-like growth factor [KO:K08523 ]
12912 Creb1; cAMP responsive element binding protein 1 [KO:K05870 ]
11909 Atf2; activating transcription factor 2 [KO:K04450 ]
11911 Atf4; activating transcription factor 4 [KO:K04374 ]
12913 Creb3; cAMP responsive element binding protein 3 [KO:K09048 ]
26427 Creb3l1; cAMP responsive element binding protein 3-like 1 [KO:K09048 ]
208647 Creb3l2; cAMP responsive element binding protein 3-like 2 [KO:K09048 ]
208677 Creb3l3; cAMP responsive element binding protein 3-like 3 [KO:K09048 ]
78284 Creb3l4; cAMP responsive element binding protein 3-like 4 [KO:K09048 ]
231991 Creb5; cAMP responsive element binding protein 5 [KO:K09047 ]
12915 Atf6b; activating transcription factor 6 beta [KO:K09049 ]
20416 Shc1; src homology 2 domain-containing transforming protein C1 [KO:K06279 ]
216148 Shc2; SHC (Src homology 2 domain containing) transforming protein 2 [KO:K17447 ]
20418 Shc3; src homology 2 domain-containing transforming protein C3 [KO:K17448 ]
271849 Shc4; SHC (Src homology 2 domain containing) family, member 4 [KO:K17449 ]
14784 Grb2; growth factor receptor bound protein 2 [KO:K04364 ]
20662 Sos1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099 ]
20663 Sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099 ]
15461 Hras; Harvey rat sarcoma virus oncogene [KO:K02833 ]
16653 Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827 ]
18706 Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
18707 Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
74769 Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
18709 Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
18708 Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
18710 Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
54393 Gabbr1; gamma-aminobutyric acid type B receptor subunit 1 [KO:K04615 ]
242425 Gabbr2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615 ]
14681 Gnao1; guanine nucleotide binding protein, alpha O [KO:K04534 ]
16519 Kcnj3; potassium inwardly-rectifying channel, subfamily J, member 3 [KO:K04997 ]
16522 Kcnj6; potassium inwardly-rectifying channel, subfamily J, member 6 [KO:K05000 ]
16524 Kcnj9; potassium inwardly-rectifying channel, subfamily J, member 9 [KO:K05002 ]
16521 Kcnj5; potassium inwardly-rectifying channel, subfamily J, member 5 [KO:K04999 ]
14682 Gnaq; guanine nucleotide binding protein, alpha q polypeptide [KO:K04634 ]
16438 Itpr1; inositol 1,4,5-trisphosphate receptor 1 [KO:K04958 ]
16439 Itpr2; inositol 1,4,5-triphosphate receptor 2 [KO:K04959 ]
16440 Itpr3; inositol 1,4,5-triphosphate receptor 3 [KO:K04960 ]
14816 Grm1; glutamate receptor, metabotropic 1 [KO:K04603 ]
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference
Authors
Zhang D, Trudeau VL
Title
Integration of membrane and nuclear estrogen receptor signaling.
Journal
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
Reference
Authors
McCarthy MM
Title
The two faces of estradiol: effects on the developing brain.
Journal
Reference
Authors
Kelly MJ, Ronnekleiv OK
Title
Membrane-initiated estrogen signaling in hypothalamic neurons.
Journal
Reference
Authors
Kelly MJ, Qiu J, Ronnekleiv OK
Title
Estrogen signaling in the hypothalamus.
Journal
Reference
Authors
Raz L, Khan MM, Mahesh VB, Vadlamudi RK, Brann DW
Title
Rapid estrogen signaling in the brain.
Journal
Reference
Authors
Malyala A, Kelly MJ, Ronnekleiv OK
Title
Estrogen modulation of hypothalamic neurons: activation of multiple signaling pathways and gene expression changes.
Journal
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
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
Reference
Authors
Meyer MR, Haas E, Prossnitz ER, Barton M
Title
Non-genomic regulation of vascular cell function and growth by estrogen.
Journal
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
Reference
Authors
Bjornstrom L, Sjoberg M
Title
Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes.
Journal
Reference
Authors
Manavathi B, Kumar R
Title
Steering estrogen signals from the plasma membrane to the nucleus: two sides of the coin.
Journal
Reference
Authors
Prossnitz ER, Barton M
Title
The G-protein-coupled estrogen receptor GPER in health and disease.
Journal
Reference
Authors
Meyer MR, Prossnitz ER, Barton M
Title
The G protein-coupled estrogen receptor GPER/GPR30 as a regulator of cardiovascular function.
Journal
Reference
Authors
Maggiolini M, Picard D
Title
The unfolding stories of GPR30, a new membrane-bound estrogen receptor.
Journal
Reference
Authors
Prossnitz ER, Maggiolini M
Title
Mechanisms of estrogen signaling and gene expression via GPR30.
Journal
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
Reference
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
Reference
Authors
Razandi M, Pedram A, Park ST, Levin ER
Title
Proximal events in signaling by plasma membrane estrogen receptors.
Journal
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
Reference
Authors
Thomas C, Gustafsson JA
Title
The different roles of ER subtypes in cancer biology and therapy.
Journal
Related pathway
mmu04270 Vascular smooth muscle contraction
KO pathway
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