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The Phosphorylation of PDX-1 by Protein Kinase CK2 Is Crucial for Its Stability
The homeodomain protein PDX-1 is a critical regulator of pancreatic development and insulin production in pancreatic β-cells. We have recently shown that PDX-1 is a substrate of protein kinase CK2; a multifunctional protein kinase which is implicated in the regulation of various cellular aspects, su...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374406/ https://www.ncbi.nlm.nih.gov/pubmed/28036027 http://dx.doi.org/10.3390/ph10010002 |
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author | Klein, Sabrina Meng, Rui Montenarh, Mathias Götz, Claudia |
author_facet | Klein, Sabrina Meng, Rui Montenarh, Mathias Götz, Claudia |
author_sort | Klein, Sabrina |
collection | PubMed |
description | The homeodomain protein PDX-1 is a critical regulator of pancreatic development and insulin production in pancreatic β-cells. We have recently shown that PDX-1 is a substrate of protein kinase CK2; a multifunctional protein kinase which is implicated in the regulation of various cellular aspects, such as differentiation, proliferation, and survival. The CK2 phosphorylation site of PDX-1 is located within the binding region of the E3 ubiquitin ligase adaptor protein PCIF1. To study the interaction between PDX-1 and PCIF1 we used immunofluorescence analysis, co-immunoprecipitation, GST-pull-down studies, and proximity ligation assay (PLA). For the analysis of the stability of PDX-1 we performed a cycloheximide chase. We used PDX-1 in its wild-type form as well as phosphomutants of the CK2 phosphorylation site. In pancreatic β-cells PDX-1 binds to PCIF1. The phosphorylation of PDX-1 by CK2 increases the ratio of PCIF1 bound to PDX-1. The stability of PDX-1 is extended in the absence of CK2 phosphorylation. Our results identified protein kinase CK2 as new important modulator of the stability of PDX-1. |
format | Online Article Text |
id | pubmed-5374406 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-53744062017-04-10 The Phosphorylation of PDX-1 by Protein Kinase CK2 Is Crucial for Its Stability Klein, Sabrina Meng, Rui Montenarh, Mathias Götz, Claudia Pharmaceuticals (Basel) Article The homeodomain protein PDX-1 is a critical regulator of pancreatic development and insulin production in pancreatic β-cells. We have recently shown that PDX-1 is a substrate of protein kinase CK2; a multifunctional protein kinase which is implicated in the regulation of various cellular aspects, such as differentiation, proliferation, and survival. The CK2 phosphorylation site of PDX-1 is located within the binding region of the E3 ubiquitin ligase adaptor protein PCIF1. To study the interaction between PDX-1 and PCIF1 we used immunofluorescence analysis, co-immunoprecipitation, GST-pull-down studies, and proximity ligation assay (PLA). For the analysis of the stability of PDX-1 we performed a cycloheximide chase. We used PDX-1 in its wild-type form as well as phosphomutants of the CK2 phosphorylation site. In pancreatic β-cells PDX-1 binds to PCIF1. The phosphorylation of PDX-1 by CK2 increases the ratio of PCIF1 bound to PDX-1. The stability of PDX-1 is extended in the absence of CK2 phosphorylation. Our results identified protein kinase CK2 as new important modulator of the stability of PDX-1. MDPI 2016-12-28 /pmc/articles/PMC5374406/ /pubmed/28036027 http://dx.doi.org/10.3390/ph10010002 Text en © 2016 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Klein, Sabrina Meng, Rui Montenarh, Mathias Götz, Claudia The Phosphorylation of PDX-1 by Protein Kinase CK2 Is Crucial for Its Stability |
title | The Phosphorylation of PDX-1 by Protein Kinase CK2 Is Crucial for Its Stability |
title_full | The Phosphorylation of PDX-1 by Protein Kinase CK2 Is Crucial for Its Stability |
title_fullStr | The Phosphorylation of PDX-1 by Protein Kinase CK2 Is Crucial for Its Stability |
title_full_unstemmed | The Phosphorylation of PDX-1 by Protein Kinase CK2 Is Crucial for Its Stability |
title_short | The Phosphorylation of PDX-1 by Protein Kinase CK2 Is Crucial for Its Stability |
title_sort | phosphorylation of pdx-1 by protein kinase ck2 is crucial for its stability |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374406/ https://www.ncbi.nlm.nih.gov/pubmed/28036027 http://dx.doi.org/10.3390/ph10010002 |
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