Serine/threonine protein kinase SGK1 in glucocorticoid-dependenttransdifferentiation of pancreatic acinar cells to hepatocytes
- Lookup NU author(s)
- Dr Karen Wallace
- QUAN LONG
- Emma Fairhall
- Professor Matthew Wright
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| Author(s) | | Wallace K, Long Q, Fairhall EA, Charlton KA, Wright MC |
| Publication type | | Article |
| Journal | | Journal of Cell Science |
| Year | | 2011 |
| Volume | | 124 |
| Issue | | 3 |
| Pages | | 405-413 |
| ISSN (print) | | 0021-9533 |
| ISSN (electronic) | | 1477-9137 |
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| Full text for this publication is not currently held within this repository. Alternative links are provided below where available. |
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| Elevated glucocorticoid levels result in the transdifferentiation of pancreaticacinar cells into hepatocytes through a process that requires a transientrepression of WNT signalling upstream of the induction of C/EBP-β. However, themechanism by which glucocorticoid interacts with WNT signalling is unknown. Ascreen of microarray data showed that the serine/threonine protein kinase SGK1(serum- and glucocorticoid-regulated kinase 1) was markedly induced in the model B-13 pancreatic rat acinar cell line after glucocorticoid treatment (whichconverts them into hepatocyte-like 'B-13/H' cells) and this was confirmed at the level of mRNA (notably an alternatively transcribed SGK1C form) and protein.Knockdown of SGK1 using an siRNA designed to target all variant transcriptsinhibited glucocorticoid-dependent transdifferentiation, whereas overexpressionof the human C isoform (and also the human SGK1F isoform, for which no orthologuein the rat has been identified) alone - but not the wild-type A form - inhibited distal WNT signalling Tcf/Lef transcription factor activity, and converted B-13cells into B-13/H cells. These effects were lost when the kinase functions ofSGK1C and SGK1F were mutated. Inhibition of SGK1 kinase activity also inhibitedglucocorticoid-dependent transdifferentiation. Expression of SGK1C and SGK1Fresulted in the appearance of phosphorylated β-catenin, and recombinant SGK1 was shown to directly phosphorylate purified β-catenin in vitro in an ATP-dependentreaction. These data therefore demonstrate a crucial role for SGK1 induction inB-13 cell transdifferentiation to B-13/H hepatocytes and suggest that directphosphorylation of β-catenin by SGK1C represents the mechanism of crosstalkbetween glucocorticoid and WNT signalling pathways. |
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| Publisher | | The Company of Biologists Ltd. |
| URL | | http://dx.doi.org/10.1242/jcs.077503 |
| DOI | | 10.1242/jcs.077503 |
| PubMed id | | 21224398 |
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