Pancreatic and duodenal homeobox 1 (PDX1) phosphorylation at serine-269 is HIPK2-dependent and affects PDX1 subnuclear localization.
Bottom Line: Homeodomain interacting protein kinase 2 (HIPK2) phosphorylates PDX1 in vitro; phosphate incorporation substantially decreases in PDX1 S269A mutant.Silencing of HIPK2 led to a 51+/-0.2% decrease in Ser-269 phosphorylation in MIN6 beta-cells.Mutation of Ser-269 to phosphomimetic residue glutamic acid (S269E) or de-phosphomimetic residue alanine (S269A) exerted no effect on PDX1 half-life.
Affiliation: Section of Cell Biology, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London SW7 2AZ, UK.Show MeSH
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Mentions: In order to determine whether de-phosphorylation at Ser-269 at elevated glucose concentrations may contribute to the nucleoplasmic accumulation of PDX1, MIN6 β-cells were transduced with adenoviruses encoding c-myc-tagged wild-type, S269A or S269E mutant forms of PDX1. Cells were then cultured at either 3 or 30 mM glucose. High glucose caused a significant redistribution both of the de-phosphomimetic mutant S269A PDX1 and wild-type PDX1 from nuclear periphery to nucleoplasm (Fig. 4), consistent with previous studies . Thus, at 30 mM glucose wild-type PDX1 was predominantly present in the nuclear region, as was the de-phosphomimetic mutant, while the phospho-mimetic mutant displayed a different localization (nuclear periphery) as compared to wild-type PDX1.
Affiliation: Section of Cell Biology, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London SW7 2AZ, UK.