Estrogen-independent phosphorylation of ESR1 S118 by MAPK1 and MAPK3

Stable Identifier
R-HSA-9032751
Type
Reaction [BlackBoxEvent]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

ESR1-mediated signaling can be initiated in an estrogen-independent manner downstream of stimuli such as EGF, NRG1, IGF, insulin, dopamine and cAMP (Ignar-Trowbridge et al, 1993, Pietras et al, 1995; Ma et al, 1994; Newton et al, 1994; Smith et al, 1993; Aronica and Katzenellenbogen, 1993). Stimulation with EGF or IFGF-1 promotes the MAPK-dependent phosphorylation of ESR1 at serine 118, which contributes to interaction with CBP/p300 and the p160 family of coactivators (Bunone et al, 1996; Chen et al, 2002; Cheng et al, 2007; reviewed in Anbalagan and Rowan, 2105). Serine 118 is also phosphorylated in response to estrogen stimulation (Chen et al, 2002; reviewed in Anbalagan and Rowan, 2015).
The relationship between MAPK-dependent S118 phosphorylation of ESR1 and the release from the cochaperone complex and ESR1 dimerization is not clear. In this reaction, all these events are shown happening simultaneously.

Literature References
PubMed ID Title Journal Year
12118371 Phosphorylation of human estrogen receptor alpha at serine 118 by two distinct signal transduction pathways revealed by phosphorylation-specific antisera

Chen, D, Washbrook, E, Sarwar, N, Bates, GJ, Pace, PE, Thirunuvakkarasu, V, Taylor, J, Epstein, RJ, Fuller-Pace, FV, Egly, JM, Coombes, RC, Ali, S

Oncogene 2002
8641283 Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation

Bunone, G, Briand, PA, Miksicek, RJ, Picard, D

EMBO J. 1996
7984152 Insulin-like growth factors activate estrogen receptor to control the growth and differentiation of the human neuroblastoma cell line SK-ER3

Ma, ZQ, Santagati, S, Patrone, C, Pollio, G, Vegeto, E, Maggi, A

Mol. Endocrinol. 1994
8232319 Peptide growth factors elicit estrogen receptor-dependent transcriptional activation of an estrogen-responsive element

Ignar-Trowbridge, DM, Teng, CT, Ross, KA, Parker, MG, Korach, KS, McLachlan, JA

Mol. Endocrinol. 1993
25597633 Estrogen receptor alpha phosphorylation and its functional impact in human breast cancer

Anbalagan, M, Rowan, BG

Mol. Cell. Endocrinol. 2015
17615152 A functional serine 118 phosphorylation site in estrogen receptor-alpha is required for down-regulation of gene expression by 17beta-estradiol and 4-hydroxytamoxifen

Cheng, J, Zhang, C, Shapiro, DJ

Endocrinology 2007
7689695 Stimulation of estrogen receptor-mediated transcription and alteration in the phosphorylation state of the rat uterine estrogen receptor by estrogen, cyclic adenosine monophosphate, and insulin-like growth factor-I

Aronica, SM, Katzenellenbogen, BS

Mol. Endocrinol. 1993
7784095 HER-2 tyrosine kinase pathway targets estrogen receptor and promotes hormone-independent growth in human breast cancer cells

Pietras, RJ, Arboleda, J, Reese, DM, Wongvipat, N, Pegram, MD, Ramos, L, Gorman, CM, Parker, MG, Sliwkowski, MX, Slamon, DJ

Oncogene 1995
8180109 The unliganded estrogen receptor (ER) transduces growth factor signals

Newton, CJ, Buric, R, Trapp, T, Brockmeier, S, Pagotto, U, Stalla, GK

J. Steroid Biochem. Mol. Biol. 1994
8327492 Modulation of the ligand-independent activation of the human estrogen receptor by hormone and antihormone

Smith, CL, Conneely, OM, O'Malley, BW

Proc. Natl. Acad. Sci. U.S.A. 1993
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
protein serine/threonine kinase activity of p-T,Y MAPK dimers [nucleoplasm]
Physical Entity
Activity
Orthologous Events
Authored
Reviewed