dc.creator | Humphrey, Rohan K. | |
dc.creator | Yu, Shu-Mei | |
dc.creator | Flores, Luis Emilio | |
dc.creator | Jhala, Ulupi S. | |
dc.date.accessioned | 2020-02-04T15:08:19Z | |
dc.date.accessioned | 2022-10-15T13:47:06Z | |
dc.date.available | 2020-02-04T15:08:19Z | |
dc.date.available | 2022-10-15T13:47:06Z | |
dc.date.created | 2020-02-04T15:08:19Z | |
dc.date.issued | 2010-01 | |
dc.identifier | Humphrey, Rohan K.; Yu, Shu-Mei; Flores, Luis Emilio; Jhala, Ulupi S.; Glucose regulates steady-state levels of PDX1 via the reciprocal actions of GSK3 and AKT kinases; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 285; 5; 1-2010; 3406-3416 | |
dc.identifier | 0021-9258 | |
dc.identifier | http://hdl.handle.net/11336/96675 | |
dc.identifier | CONICET Digital | |
dc.identifier | CONICET | |
dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/4393131 | |
dc.description.abstract | The pancreatic beta cell is sensitive to even small changes in PDX1 protein levels; consequently, Pdx1 haploinsufficiency can inhibit beta cell growth and decrease insulin biosynthesis and gene expression, leading to compromised glucose-stimulated insulin secretion. Using metabolic labeling of primary islets and a cultured β cell line, we show that glucose levels modulate PDX1protein phosphorylation at a novel C-terminal GSK3 consensus that maps to serines 268 and 272. A decrease in glucose levels triggers increased turnover of the PDX1 protein in a GSK3-dependent manner, such that PDX1 phosphomutants are refractory to the destabilizing effect of low glucose. Glucose-stimulated activation of AKT and inhibition of GSK3 decrease PDX1 phosphorylation and delay degradation. Furthermore, direct pharmacologic inhibition of AKT destabilizes, and inhibition of GSK3 increasesPDX1proteinstability.These studies define a novel functional role for the PDX1 C terminus in mediating the effects of glucose and demonstrate that glucose modulates PDX1 stability via the AKT-GSK3 axis. | |
dc.language | eng | |
dc.publisher | American Society for Biochemistry and Molecular Biology | |
dc.relation | info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1074/jbc.M109.006734 | |
dc.relation | info:eu-repo/semantics/altIdentifier/url/https://www.jbc.org/content/285/5/3406 | |
dc.rights | https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | Glucose | |
dc.subject | Pdx1 | |
dc.subject | AKT | |
dc.subject | GSK3 | |
dc.title | Glucose regulates steady-state levels of PDX1 via the reciprocal actions of GSK3 and AKT kinases | |
dc.type | info:eu-repo/semantics/article | |
dc.type | info:ar-repo/semantics/artículo | |
dc.type | info:eu-repo/semantics/publishedVersion | |