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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...

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Detalles Bibliográficos
Autores principales: Klein, Sabrina, Meng, Rui, Montenarh, Mathias, Götz, Claudia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
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.
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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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