ERK1/2-RSK2 Signaling in Regulation of ERα-Mediated Responses

Overview

Journal Endocrinology

Publisher Oxford University Press

Specialty Endocrinology

Date 2022 Jul 26

PMID 35880639

Authors

Deborah A Lannigan

Affiliations

Soon will be listed here.

Abstract

Signaling via extracellular regulated kinase 1/2 (ERK1/2) and p90 ribosomal S6 kinase (RSK), a downstream effector, mediates numerous processes. For example, ERK1/2-RSK signaling is essential for estrogen homeostasis in the mammary gland and uterus to maintain physiological responsiveness. This review will focus on the coordination of ERK1/2-RSK2 and estrogen signaling through estrogen receptor alpha (ERα). The interrelationship and the feedback mechanisms between these pathways occurs at the level of transcription, translation, and posttranslational modification. Identifying how ERK1/2-RSK2 and estrogen signaling cooperate in homeostasis and disease may lead to novel therapeutic approaches in estrogen-dependent disorders.

Citing Articles

Advances in research on malignant transformation of endometriosis-associated ovarian cancer.

Chen F, Zhu M, Li W Front Oncol. 2024; 14:1475231.

PMID: 39445058 PMC: 11496038. DOI: 10.3389/fonc.2024.1475231.

The Role MicroRNA-135a in Suppressing Tumor Growth in Kidney Cancer Through the Regulation of Phosphoprotein Phosphatase2A and the Activation of the AKT and ERK1/2 Signaling Pathways.

Wang K, Chen H, Chen X, Fang Z, Xiao E, Liao Q J Cancer. 2024; 15(4):999-1008.

PMID: 38230208 PMC: 10788712. DOI: 10.7150/jca.90756.

Therapeutic targeting of p90 ribosomal S6 kinase.

Wright E, Lannigan D Front Cell Dev Biol. 2024; 11:1297292.

PMID: 38169775 PMC: 10758423. DOI: 10.3389/fcell.2023.1297292.

Mitogen-Activated Protein Kinase and Nuclear Hormone Receptor Crosstalk in Cancer Immunotherapy.

Burgermeister E Int J Mol Sci. 2023; 24(17).

PMID: 37686465 PMC: 10488039. DOI: 10.3390/ijms241713661.

Structure-based drug design-guided identification of estrogen receptor binders.

Samanta R, Pradhan K, Sen D, Kar S, Ghosh M Mol Divers. 2023; 28(3):1291-1303.

PMID: 37289383 DOI: 10.1007/s11030-023-10657-z.

References

Arao Y, Hamilton K, Lierz S, Korach K . N-terminal transactivation function, AF-1, of estrogen receptor alpha controls obesity through enhancement of energy expenditure. Mol Metab. 2018; 18:68-78. PMC: 6308972. DOI: 10.1016/j.molmet.2018.09.006. View

Smith J, Poteet-Smith C, Xu Y, Errington T, Hecht S, Lannigan D . Identification of the first specific inhibitor of p90 ribosomal S6 kinase (RSK) reveals an unexpected role for RSK in cancer cell proliferation. Cancer Res. 2005; 65(3):1027-34. View

Unal E, Uhlitz F, Bluthgen N . A compendium of ERK targets. FEBS Lett. 2017; 591(17):2607-2615. DOI: 10.1002/1873-3468.12740. View

Freed D, Bessman N, Kiyatkin A, Salazar-Cavazos E, Byrne P, Moore J . EGFR Ligands Differentially Stabilize Receptor Dimers to Specify Signaling Kinetics. Cell. 2017; 171(3):683-695.e18. PMC: 5650921. DOI: 10.1016/j.cell.2017.09.017. View

Huang Y, Ognjenovic J, Karandur D, Miller K, Merk A, Subramaniam S . A molecular mechanism for the generation of ligand-dependent differential outputs by the epidermal growth factor receptor. Elife. 2021; 10. PMC: 8716103. DOI: 10.7554/eLife.73218. View

Pages G, Guerin S, Grall D, Bonino F, Smith A, Anjuere F . Defective thymocyte maturation in p44 MAP kinase (Erk 1) knockout mice. Science. 1999; 286(5443):1374-7. DOI: 10.1126/science.286.5443.1374. View

Yamashita H, Takahashi S, Ito Y, Yamashita T, Ando Y, Toyama T . Predictors of response to exemestane as primary endocrine therapy in estrogen receptor-positive breast cancer. Cancer Sci. 2009; 100(11):2028-33. PMC: 11158316. DOI: 10.1111/j.1349-7006.2009.01274.x. View

Mal R, Magner A, David J, Datta J, Vallabhaneni M, Kassem M . Estrogen Receptor Beta (ERβ): A Ligand Activated Tumor Suppressor. Front Oncol. 2020; 10:587386. PMC: 7645238. DOI: 10.3389/fonc.2020.587386. View

Ludwik K, McDonald O, Brenin D, Lannigan D . ERα-Mediated Nuclear Sequestration of RSK2 Is Required for ER Breast Cancer Tumorigenesis. Cancer Res. 2018; 78(8):2014-2025. PMC: 9011919. DOI: 10.1158/0008-5472.CAN-17-2063. View

10.

Hewitt S, Korach K . Estrogen Receptors: New Directions in the New Millennium. Endocr Rev. 2018; 39(5):664-675. PMC: 6173474. DOI: 10.1210/er.2018-00087. View

11.

Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H . Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science. 1995; 270(5241):1491-4. DOI: 10.1126/science.270.5241.1491. View

12.

Therrien M, Chang H, Solomon N, Karim F, Wassarman D, Rubin G . KSR, a novel protein kinase required for RAS signal transduction. Cell. 1995; 83(6):879-88. DOI: 10.1016/0092-8674(95)90204-x. View

13.

Razidlo G, Kortum R, Haferbier J, Lewis R . Phosphorylation regulates KSR1 stability, ERK activation, and cell proliferation. J Biol Chem. 2004; 279(46):47808-14. DOI: 10.1074/jbc.M406395200. View

14.

Houles T, Roux P . Defining the role of the RSK isoforms in cancer. Semin Cancer Biol. 2017; 48:53-61. DOI: 10.1016/j.semcancer.2017.04.016. View

15.

Suresh P, Tsutsumi R, Venkatesh T . YBX1 at the crossroads of non-coding transcriptome, exosomal, and cytoplasmic granular signaling. Eur J Cell Biol. 2018; 97(3):163-167. DOI: 10.1016/j.ejcb.2018.02.003. View

16.

Fischer M, Raabe T . Animal Models for Coffin-Lowry Syndrome: RSK2 and Nervous System Dysfunction. Front Behav Neurosci. 2018; 12:106. PMC: 5974046. DOI: 10.3389/fnbeh.2018.00106. View

17.

Ludwik K, Campbell J, Li M, Li Y, Sandusky Z, Pasic L . Development of a RSK Inhibitor as a Novel Therapy for Triple-Negative Breast Cancer. Mol Cancer Ther. 2016; 15(11):2598-2608. PMC: 5807013. DOI: 10.1158/1535-7163.MCT-16-0106. View

18.

Fuentes N, Silveyra P . Estrogen receptor signaling mechanisms. Adv Protein Chem Struct Biol. 2019; 116:135-170. PMC: 6533072. DOI: 10.1016/bs.apcsb.2019.01.001. View

19.

Ludwik K, Sandusky Z, Stauffer K, Li Y, Boyd K, ODoherty G . RSK2 Maintains Adult Estrogen Homeostasis by Inhibiting ERK1/2-Mediated Degradation of Estrogen Receptor Alpha. Cell Rep. 2020; 32(3):107931. PMC: 7465694. DOI: 10.1016/j.celrep.2020.107931. View

20.

Rooney A, van der Meulen M . Mouse models to evaluate the role of estrogen receptor α in skeletal maintenance and adaptation. Ann N Y Acad Sci. 2017; 1410(1):85-92. DOI: 10.1111/nyas.13523. View