Activation of protein synthesis in mouse uterine epithelial cells by estradiol-17β is mediated by a PKC-ERK1/2-mTOR signaling pathway

Proceedings of the National Academy of Sciences of the United States of America
Yuxiang WangJeffrey W Pollard

Abstract

The uterine epithelium of mice and humans undergoes cyclical waves of cell proliferation and differentiation under the regulation of estradiol-17β (E2) and progesterone (P4). These epithelial cells respond to E2 with increased protein and DNA synthesis, whereas P4 inhibits only the E2-induced DNA synthetic response. Here we show that E2 regulates protein synthesis in these epithelial cells through activating PKC that in turn stimulates ERK1/2 to phosphorylate and thereby activate the central regulator of protein synthesis mechanistic target of rapamycin (mTOR). This mTOR pathway is not inhibited by P4. Inhibitor studies with an estrogen receptor (ESR1) antagonist showed the dependence of this mTOR pathway on ESR1 but that once activated, a phosphorylation cascade independent of ESR1 propagates the pathway. E2 also stimulates an IGF1 receptor (IGF1R) to PI3 kinase to AKT to GSK-3β pathway required for activation of the canonical cell cycle machinery that is inhibited by P4. PKC activation did not stimulate this pathway nor does inhibition of PKC or ERK1/2 affect it. These studies therefore indicate a mechanism whereby DNA and protein synthesis are regulated by two ESR1-activated pathways that run in parallel with only the one re...Continue Reading

References

Nov 1, 1979·Journal of Reproduction and Fertility·B FaggV E Quarmby
Apr 1, 1976·The Journal of Endocrinology·L MartinB Fagg
Jan 1, 1985·Experimental Cell Research·R F Brooks, R Shields
Apr 1, 1973·Proceedings of the National Academy of Sciences of the United States of America·J A Smith, L Martin
Oct 3, 2001·Physiological Reviews·S NilssonJ A Gustafsson
Dec 13, 2005·The Journal of Biological Chemistry·Luowei LiStuart H Yuspa
Sep 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·Haiyan PanJeffrey W Pollard
Sep 27, 2007·Proceedings of the National Academy of Sciences of the United States of America·Liyin Zhu, Jeffrey W Pollard
Nov 28, 2007·Annual Review of Pathology·Antonio Di Cristofano, Lora Hedrick Ellenson
Apr 3, 2009·Nature Reviews. Molecular Cell Biology·Xiaoju Max Ma, John Blenis
Dec 18, 2009·The FEBS Journal·Riaan ConradieJacky L Snoep
Oct 27, 2010·Proceedings of the National Academy of Sciences of the United States of America·Wipawee WinuthayanonKenneth S Korach
Sep 6, 2011·Nature Cell Biology·Maria M Mihaylova, Reuben J Shaw
Nov 26, 2011·Molecular and Cellular Endocrinology·Margeaux Wetendorf, Francesco J DeMayo
Apr 17, 2012·Cell·Mathieu Laplante, David M Sabatini
Apr 28, 2012·Proceedings of the National Academy of Sciences of the United States of America·Sanhita Ray, Jeffrey W Pollard
Jul 24, 2012·Fertility and Sterility·Richard O Burney, Linda C Giudice
May 4, 2013·Journal of Cell Science·Mathieu Laplante, David M Sabatini
Jul 25, 2014·The American Journal of Pathology·Takiko DaikokuSudhansu K Dey

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Citations

Jan 19, 2016·Frontiers in Endocrinology·Jonathan A SobelGeraldine O Canny
Aug 7, 2017·Reproduction : the Official Journal of the Society for the Study of Fertility·Seo-Ho LeeUh-Hyun Kim
Aug 2, 2018·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Hee Jin SonYoung-Joon Surh
Apr 6, 2019·Reproduction : the Official Journal of the Society for the Study of Fertility·Vinay ShuklaAnila Dwivedi
Dec 17, 2016·Oncotarget·Preety BajwaPradeep S Tanwar
Dec 12, 2018·Molecular Medicine Reports·Junrong ZouDeqiang Huang
Sep 4, 2020·Biological & Pharmaceutical Bulletin·Tomoyasu FujiiTetsuo Morita
Aug 25, 2017·Proceedings of the National Academy of Sciences of the United States of America·Fiamma SalernoMonika C Wolkers
Nov 15, 2017·Nature Communications·Mei YuDemin Wang
Dec 12, 2018·Journal of Cellular Physiology·Naser ShokrzadehBehrooz Niknafs
Oct 28, 2019·Frontiers in Endocrinology·Zaixin Guo, Qi Yu
Feb 9, 2017·Archives of Gynecology and Obstetrics·Alexander FreisAriane Germeyer
Jul 9, 2020·Apoptosis : an International Journal on Programmed Cell Death·Mehrdad GhashghaeiniaMartin Köberle

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