Nuclear Entry of Activated MAPK Is Restricted in Primary Ovarian and Mammary Epithelial Cells

Elizabeth R. Smith, Kathy Qi Cai, Jennifer L. Smedberg, Melina M. Ribeiro, Malgorzata E. Rula, Carolyn Slater, Andrew K. Godwin, Xiangxi Xu

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background: 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.Principal Findings: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. Conclusion: 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.

Original languageEnglish
Article numbere0009295
JournalPLoS One
Volume5
Issue number2
DOIs
StatePublished - Dec 1 2010

Fingerprint

Nuclear Pore Complex Proteins
Karyopherins
Phosphorylation
Transcription
breasts
Breast
epithelial cells
Epithelial Cells
Chemical activation
Cells
Protein-Serine-Threonine Kinases
Mitogen-Activated Protein Kinase Kinases
importins
nucleoporins
imports
Small Interfering RNA
Assays
cells
mitogen-activated protein kinase
Cell Nucleus Active Transport

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Smith, E. R., Cai, K. Q., Smedberg, J. L., Ribeiro, M. M., Rula, M. E., Slater, C., ... Xu, X. (2010). Nuclear Entry of Activated MAPK Is Restricted in Primary Ovarian and Mammary Epithelial Cells. PLoS One, 5(2), [e0009295]. https://doi.org/10.1371/journal.pone.0009295

Nuclear Entry of Activated MAPK Is Restricted in Primary Ovarian and Mammary Epithelial Cells. / Smith, Elizabeth R.; Cai, Kathy Qi; Smedberg, Jennifer L.; Ribeiro, Melina M.; Rula, Malgorzata E.; Slater, Carolyn; Godwin, Andrew K.; Xu, Xiangxi.

In: PLoS One, Vol. 5, No. 2, e0009295, 01.12.2010.

Research output: Contribution to journalArticle

Smith, ER, Cai, KQ, Smedberg, JL, Ribeiro, MM, Rula, ME, Slater, C, Godwin, AK & Xu, X 2010, 'Nuclear Entry of Activated MAPK Is Restricted in Primary Ovarian and Mammary Epithelial Cells', PLoS One, vol. 5, no. 2, e0009295. https://doi.org/10.1371/journal.pone.0009295
Smith ER, Cai KQ, Smedberg JL, Ribeiro MM, Rula ME, Slater C et al. Nuclear Entry of Activated MAPK Is Restricted in Primary Ovarian and Mammary Epithelial Cells. PLoS One. 2010 Dec 1;5(2). e0009295. https://doi.org/10.1371/journal.pone.0009295
Smith, Elizabeth R. ; Cai, Kathy Qi ; Smedberg, Jennifer L. ; Ribeiro, Melina M. ; Rula, Malgorzata E. ; Slater, Carolyn ; Godwin, Andrew K. ; Xu, Xiangxi. / Nuclear Entry of Activated MAPK Is Restricted in Primary Ovarian and Mammary Epithelial Cells. In: PLoS One. 2010 ; Vol. 5, No. 2.
@article{ac55a171d6784699b3e188bb900edcf9,
title = "Nuclear Entry of Activated MAPK Is Restricted in Primary Ovarian and Mammary Epithelial Cells",
abstract = "Background: 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.Principal Findings: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. Conclusion: 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.",
author = "Smith, {Elizabeth R.} and Cai, {Kathy Qi} and Smedberg, {Jennifer L.} and Ribeiro, {Melina M.} and Rula, {Malgorzata E.} and Carolyn Slater and Godwin, {Andrew K.} and Xiangxi Xu",
year = "2010",
month = "12",
day = "1",
doi = "10.1371/journal.pone.0009295",
language = "English",
volume = "5",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

TY - JOUR

T1 - Nuclear Entry of Activated MAPK Is Restricted in Primary Ovarian and Mammary Epithelial Cells

AU - Smith, Elizabeth R.

AU - Cai, Kathy Qi

AU - Smedberg, Jennifer L.

AU - Ribeiro, Melina M.

AU - Rula, Malgorzata E.

AU - Slater, Carolyn

AU - Godwin, Andrew K.

AU - Xu, Xiangxi

PY - 2010/12/1

Y1 - 2010/12/1

N2 - Background: 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.Principal Findings: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. Conclusion: 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.

AB - Background: 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.Principal Findings: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. Conclusion: 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.

UR - http://www.scopus.com/inward/record.url?scp=77957291965&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957291965&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0009295

DO - 10.1371/journal.pone.0009295

M3 - Article

C2 - 20174585

AN - SCOPUS:77957291965

VL - 5

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 2

M1 - e0009295

ER -