Nuclear entry of activated MAPK is restricted in primary ovarian and mammary epithelial cells.

<h4>Background</h4>The MAPK/ERK1/2 serine kinases are primary mediators of the Ras mitogenic signaling pathway. Phosphorylation by MEK activates MAPK/ERK in the cytoplasm, and phospho-ERK is thought to enter the nucleus readily to modulate transcription.<h4>Principal findings</h...

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Autores principales:	Elizabeth R Smith, Kathy Qi Cai, Jennifer L Smedberg, Melina M Ribeiro, Malgorzata E Rula, Carolyn Slater, Andrew K Godwin, Xiang-Xi Xu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e43d119556a844cd96b1497f8ebd8888
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spelling	oai:doaj.org-article:e43d119556a844cd96b1497f8ebd88882021-11-25T06:25:45ZNuclear entry of activated MAPK is restricted in primary ovarian and mammary epithelial cells.1932-620310.1371/journal.pone.0009295https://doaj.org/article/e43d119556a844cd96b1497f8ebd88882010-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20174585/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The MAPK/ERK1/2 serine kinases are primary mediators of the Ras mitogenic signaling pathway. Phosphorylation by MEK activates MAPK/ERK in the cytoplasm, and phospho-ERK is thought to enter the nucleus readily to modulate transcription.<h4>Principal findings</h4>Here, however, we observe that in primary cultures of breast and ovarian epithelial cells, phosphorylation and activation of ERK1/2 are disassociated from nuclear translocalization and transcription of downstream targets, such as c-Fos, suggesting that nuclear translocation is limited in primary cells. Accordingly, in import assays in vitro, primary cells showed a lower import activity for ERK1/2 than cancer cells, in which activated MAPK readily translocated into the nucleus and activated c-Fos expression. Primary cells express lower levels of nuclear pore complex proteins and the nuclear transport factors, importin B1 and importin 7, which may explain the limiting ERK1/2 import found in primary cells. Additionally, reduction in expression of nucleoporin 153 by siRNA targeting reduced ERK1/2 nuclear activity in cancer cells.<h4>Conclusion</h4>ERK1/2 activation is dissociated from nuclear entry, which is a rate limiting step in primary cells and in vivo, and the restriction of nuclear entry is disrupted in transformed cells by the increased expression of nuclear pores and/or nuclear transport factors.Elizabeth R SmithKathy Qi CaiJennifer L SmedbergMelina M RibeiroMalgorzata E RulaCarolyn SlaterAndrew K GodwinXiang-Xi XuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 2, p e9295 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elizabeth R Smith Kathy Qi Cai Jennifer L Smedberg Melina M Ribeiro Malgorzata E Rula Carolyn Slater Andrew K Godwin Xiang-Xi Xu Nuclear entry of activated MAPK is restricted in primary ovarian and mammary epithelial cells.
description	<h4>Background</h4>The MAPK/ERK1/2 serine kinases are primary mediators of the Ras mitogenic signaling pathway. Phosphorylation by MEK activates MAPK/ERK in the cytoplasm, and phospho-ERK is thought to enter the nucleus readily to modulate transcription.<h4>Principal findings</h4>Here, however, we observe that in primary cultures of breast and ovarian epithelial cells, phosphorylation and activation of ERK1/2 are disassociated from nuclear translocalization and transcription of downstream targets, such as c-Fos, suggesting that nuclear translocation is limited in primary cells. Accordingly, in import assays in vitro, primary cells showed a lower import activity for ERK1/2 than cancer cells, in which activated MAPK readily translocated into the nucleus and activated c-Fos expression. Primary cells express lower levels of nuclear pore complex proteins and the nuclear transport factors, importin B1 and importin 7, which may explain the limiting ERK1/2 import found in primary cells. Additionally, reduction in expression of nucleoporin 153 by siRNA targeting reduced ERK1/2 nuclear activity in cancer cells.<h4>Conclusion</h4>ERK1/2 activation is dissociated from nuclear entry, which is a rate limiting step in primary cells and in vivo, and the restriction of nuclear entry is disrupted in transformed cells by the increased expression of nuclear pores and/or nuclear transport factors.
format	article
author	Elizabeth R Smith Kathy Qi Cai Jennifer L Smedberg Melina M Ribeiro Malgorzata E Rula Carolyn Slater Andrew K Godwin Xiang-Xi Xu
author_facet	Elizabeth R Smith Kathy Qi Cai Jennifer L Smedberg Melina M Ribeiro Malgorzata E Rula Carolyn Slater Andrew K Godwin Xiang-Xi Xu
author_sort	Elizabeth R Smith
title	Nuclear entry of activated MAPK is restricted in primary ovarian and mammary epithelial cells.
title_short	Nuclear entry of activated MAPK is restricted in primary ovarian and mammary epithelial cells.
title_full	Nuclear entry of activated MAPK is restricted in primary ovarian and mammary epithelial cells.
title_fullStr	Nuclear entry of activated MAPK is restricted in primary ovarian and mammary epithelial cells.
title_full_unstemmed	Nuclear entry of activated MAPK is restricted in primary ovarian and mammary epithelial cells.
title_sort	nuclear entry of activated mapk is restricted in primary ovarian and mammary epithelial cells.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/e43d119556a844cd96b1497f8ebd8888
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Nuclear entry of activated MAPK is restricted in primary ovarian and mammary epithelial cells.

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