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Nik-related kinase regulates trophoblast proliferation and placental development by modulating AKT phosphorylation
Nik-related kinase (Nrk) is a Ser/Thr kinase and was initially discovered as a molecule that was predominantly detected in skeletal muscles during development. A recent study using Nrk-null mice suggested the importance of Nrk in proper placental development; however, the molecular mechanism remains...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289614/ https://www.ncbi.nlm.nih.gov/pubmed/28152035 http://dx.doi.org/10.1371/journal.pone.0171503 |
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author | Morioka, Yuka Nam, Jin-Min Ohashi, Takashi |
author_facet | Morioka, Yuka Nam, Jin-Min Ohashi, Takashi |
author_sort | Morioka, Yuka |
collection | PubMed |
description | Nik-related kinase (Nrk) is a Ser/Thr kinase and was initially discovered as a molecule that was predominantly detected in skeletal muscles during development. A recent study using Nrk-null mice suggested the importance of Nrk in proper placental development; however, the molecular mechanism remains unknown. In this study, we demonstrated that differentiated trophoblasts from murine embryonic stem cells (ESCs) endogenously expressed Nrk and that Nrk disruption led to the enhanced proliferation of differentiated trophoblasts. This phenomenon may reflect the overproliferation of trophoblasts that has been reported in enlarged placentas of Nrk-null mice. Furthermore, we demonstrated that AKT phosphorylation at Ser473 was upregulated in Nrk-null trophoblasts and that inhibition of AKT phosphorylation cancelled the enhanced proliferation observed in differentiated Nrk-null trophoblasts. These results indicated that the upregulation of AKT phosphorylation was the possible cause of enhanced proliferation observed in Nrk-null trophoblasts. The upregulation of AKT phosphorylation was also confirmed in enlarged Nrk-null placentas in vivo, suggesting that proper regulation of AKT by Nrk was important for normal placental development. In addition, our detailed analysis on phosphorylation status of AKT isoforms in newly established trophoblast stem cells (TSCs) revealed that different levels of upregulation of AKT phosphorylation were occurred in Nrk-null TSCs depending on AKT isoforms. These results further support the importance of Nrk in proper development of trophoblast lineage cells and indicate the possible application of TSCs for the analysis of differently regulated activation mechanisms of AKT isoforms. |
format | Online Article Text |
id | pubmed-5289614 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-52896142017-02-17 Nik-related kinase regulates trophoblast proliferation and placental development by modulating AKT phosphorylation Morioka, Yuka Nam, Jin-Min Ohashi, Takashi PLoS One Research Article Nik-related kinase (Nrk) is a Ser/Thr kinase and was initially discovered as a molecule that was predominantly detected in skeletal muscles during development. A recent study using Nrk-null mice suggested the importance of Nrk in proper placental development; however, the molecular mechanism remains unknown. In this study, we demonstrated that differentiated trophoblasts from murine embryonic stem cells (ESCs) endogenously expressed Nrk and that Nrk disruption led to the enhanced proliferation of differentiated trophoblasts. This phenomenon may reflect the overproliferation of trophoblasts that has been reported in enlarged placentas of Nrk-null mice. Furthermore, we demonstrated that AKT phosphorylation at Ser473 was upregulated in Nrk-null trophoblasts and that inhibition of AKT phosphorylation cancelled the enhanced proliferation observed in differentiated Nrk-null trophoblasts. These results indicated that the upregulation of AKT phosphorylation was the possible cause of enhanced proliferation observed in Nrk-null trophoblasts. The upregulation of AKT phosphorylation was also confirmed in enlarged Nrk-null placentas in vivo, suggesting that proper regulation of AKT by Nrk was important for normal placental development. In addition, our detailed analysis on phosphorylation status of AKT isoforms in newly established trophoblast stem cells (TSCs) revealed that different levels of upregulation of AKT phosphorylation were occurred in Nrk-null TSCs depending on AKT isoforms. These results further support the importance of Nrk in proper development of trophoblast lineage cells and indicate the possible application of TSCs for the analysis of differently regulated activation mechanisms of AKT isoforms. Public Library of Science 2017-02-02 /pmc/articles/PMC5289614/ /pubmed/28152035 http://dx.doi.org/10.1371/journal.pone.0171503 Text en © 2017 Morioka et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Morioka, Yuka Nam, Jin-Min Ohashi, Takashi Nik-related kinase regulates trophoblast proliferation and placental development by modulating AKT phosphorylation |
title | Nik-related kinase regulates trophoblast proliferation and placental development by modulating AKT phosphorylation |
title_full | Nik-related kinase regulates trophoblast proliferation and placental development by modulating AKT phosphorylation |
title_fullStr | Nik-related kinase regulates trophoblast proliferation and placental development by modulating AKT phosphorylation |
title_full_unstemmed | Nik-related kinase regulates trophoblast proliferation and placental development by modulating AKT phosphorylation |
title_short | Nik-related kinase regulates trophoblast proliferation and placental development by modulating AKT phosphorylation |
title_sort | nik-related kinase regulates trophoblast proliferation and placental development by modulating akt phosphorylation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289614/ https://www.ncbi.nlm.nih.gov/pubmed/28152035 http://dx.doi.org/10.1371/journal.pone.0171503 |
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