Estrogen-independent phosphorylation of ESR1 S118 by MAPK1 and MAPK3

Stable Identifier
Reaction [omitted]
Homo sapiens
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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
8641283 Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation

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

EMBO J. 1996
12118371 Phosphorylation of human estrogen receptor alpha at serine 118 by two distinct signal transduction pathways revealed by phosphorylation-specific antisera

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

Oncogene 2002
7984152 Insulin-like growth factors activate estrogen receptor to control the growth and differentiation of the human neuroblastoma cell line SK-ER3

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

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

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

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

Rowan, BG, Anbalagan, M

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

Zhang, C, Cheng, J, 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

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

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

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

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

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

Proc. Natl. Acad. Sci. U.S.A. 1993
Catalyst Activity

protein serine/threonine kinase activity of p-T,Y MAPK dimers [nucleoplasm]

Orthologous Events
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