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 language | English |
|---|---|
| Article number | e0009295 |
| Journal | PLoS One |
| Volume | 5 |
| Issue number | 2 |
| DOIs | |
| State | Published - Dec 1 2010 |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
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 journal › Article
}
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 -