Entry
Name
Estrogen signaling pathway - Sciurus carolinensis (gray squirrel)
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
Sciurus carolinensis (gray squirrel) [GN:
ncar ]
Gene
124959781 LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283 ]
124967534 receptor-binding cancer antigen expressed on SiSo cells [KO:K22455 ]
124990886 LOW QUALITY PROTEIN: keratin, type I cytoskeletal 19-like [KO:K07604 ]
124979271 LOW QUALITY PROTEIN: keratin, type I cytoskeletal 39-like [KO:K07604 ]
124975134 guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632 ]
124979032 cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
124979831 LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-2-like [KO:K04450 ]
124991113 cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048 ]
124958938 cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048 ]
124984689 cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
124969564 cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
124964377 cyclic AMP-responsive element-binding protein 3-like isoform X1 [KO:K09048 ]
124991182 cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
124988573 cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
124963509 phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
124986648 phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
124968815 phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
124988516 gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615 ]
124992673 guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
124988012 guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630 ]
124991078 guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
124967520 guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534 ]
124980509 G protein-activated inward rectifier potassium channel 1 [KO:K04997 ]
124993028 G protein-activated inward rectifier potassium channel 2 [KO:K05000 ]
124990924 G protein-activated inward rectifier potassium channel 3 [KO:K05002 ]
124960772 G protein-activated inward rectifier potassium channel 4 isoform X1 [KO:K04999 ]
124964255 guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
124970932 inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958 ]
124983533 inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959 ]
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
KO pathway
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