The transcription factor PDX-1 (pancreatic duodenal homeobox-1) is required for normal pancreatic development and for the function of insulin-producing islet β-cells in mammals. We have shown previously that glucose regulates insulin gene expression in part through the activation and translocation of PDX-1 from the nuclear periphery to the nucleoplasm. We have also found that PASK [PAS (Per-Arnt-Sim) kinase], a member of the nutrient-regulated family of protein kinases, is activated in response to glucose challenge in β-cells and is involved in the regulation of expression of PDX-1. Purified PASK efficiently phosphorylated recombinant PDX-1 in vitro on a single site (Thr-152). To determine the impact of phosphorylation at this site, we generated wild-type and mutant (T152A, T152D and T152E) forms of PDX-1 and examined the distribution of each of these in clonal MIN6 β-cells by immunocytochemical analysis. Unexpectedly, only the T152D mutation significantly affected subcellular distribution, increasing the ratio of nuclear/cytosolic labelling at low and high glucose concentrations, suggesting that phosphorylation at Thr-152 inhibits nuclear uptake in response to glucose. Based on these results, experiments to examine the contribution of Thr-152 to the overall phosphorylation of PDX-1 in intact cells will be undertaken.
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Conference Article|
October 25 2006
Regulation by Per-Arnt-Sim (PAS) kinase of pancreatic duodenal homeobox-1 nuclear import in pancreatic β-cells
R. An;
*Henry Wellcome Signalling Laboratories and Department of Biochemistry, University of Bristol, Bristol BS8 ITD, U.K.
†Department of Cell Biology, Division of Medicine, Faculty of Medicine, Imperial College, Exhibition Road, London SW7 2AZ, U.K.
1To whom correspondence should be sent at the present address: Department of Cell Biology, Division of Medicine, Faculty of Medicine, Imperial College, Exhibition Road, London SW7 2AZ, U.K. (email g.rutter@imperial.ac.uk).
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G. da Silva Xavier;
G. da Silva Xavier
2
*Henry Wellcome Signalling Laboratories and Department of Biochemistry, University of Bristol, Bristol BS8 ITD, U.K.
†Department of Cell Biology, Division of Medicine, Faculty of Medicine, Imperial College, Exhibition Road, London SW7 2AZ, U.K.
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H.-X. Hao;
H.-X. Hao
2
‡Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84132, U.S.A.
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F. Semplici;
F. Semplici
*Henry Wellcome Signalling Laboratories and Department of Biochemistry, University of Bristol, Bristol BS8 ITD, U.K.
†Department of Cell Biology, Division of Medicine, Faculty of Medicine, Imperial College, Exhibition Road, London SW7 2AZ, U.K.
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J. Rutter;
J. Rutter
‡Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84132, U.S.A.
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G.A. Rutter
G.A. Rutter
*Henry Wellcome Signalling Laboratories and Department of Biochemistry, University of Bristol, Bristol BS8 ITD, U.K.
†Department of Cell Biology, Division of Medicine, Faculty of Medicine, Imperial College, Exhibition Road, London SW7 2AZ, U.K.
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Publisher: Portland Press Ltd
Received:
July 11 2006
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2006 The Biochemical Society
2006
Biochem Soc Trans (2006) 34 (5): 791–793.
Article history
Received:
July 11 2006
Citation
R. An, G. da Silva Xavier, H.-X. Hao, F. Semplici, J. Rutter, G.A. Rutter; Regulation by Per-Arnt-Sim (PAS) kinase of pancreatic duodenal homeobox-1 nuclear import in pancreatic β-cells. Biochem Soc Trans 1 October 2006; 34 (5): 791–793. doi: https://doi.org/10.1042/BST0340791
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