Toggle Main Menu Toggle Search

Open Access padlockePrints

Serine/threonine protein kinase SGK1 in glucocorticoid-dependent transdifferentiation of pancreatic acinar cells to hepatocytes

Lookup NU author(s): Dr Karen Wallace, QUAN LONG, Dr Emma Fairhall, Professor Matthew Wright

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

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.


Publication metadata

Author(s): Wallace K, Long Q, Fairhall EA, Charlton KA, Wright MC

Publication type: Article

Publication status: Published

Journal: Journal of Cell Science

Year: 2011

Volume: 124

Issue: 3

Pages: 405-413

Print publication date: 11/01/2011

ISSN (print): 0021-9533

ISSN (electronic): 1477-9137

Publisher: The Company of Biologists Ltd.

URL: http://dx.doi.org/10.1242/jcs.077503

DOI: 10.1242/jcs.077503

PubMed id: 21224398


Altmetrics

Altmetrics provided by Altmetric


Share