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O-GlcNAc modulation at Akt1 Ser473 correlates with apoptosis of murine pancreatic β cells

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Authors
Lee, Jung Weon; Kang, Eun-Sil; Han, Dohyun; Park, Jungeun; Kwak, Tae Kyoung; Oh, Min-A; Lee, Sin-Ae; Choi, Suyong; Park, Zee Yong; Kim, Youngsoo
Issue Date
2008
Publisher
Elsevier
Citation
Exp.Cell Res. 314(2008) 2238-2248
Keywords
Apoptosis; Akt; Posttranslational modification; Phosphorylation; O-glycosylation
Abstract
O-GlcNAc transferase (OGT)-mediated modification of protein Ser/Thr residues withO-GlcNAc influences protein activity, similar to the effects of phosphorylation. The anti-apoptotic Akt1 is both activated by phosphorylation and modified with O-GlcNAc. However, the nature and significance of the Akt1 O-GlcNAc modification is unknown. The relationship of O-GlcNAc modification and phosphorylation at Akt1 Ser473 was examined with respect to apoptosis of murine β-pancreatic cells. Glucosamine treatment induced apoptosis, which correlated with enhanced O-GlcNAc modification of Akt1 and concomitant reduction in Ser473 phosphorylation. Pharmacological inhibition of OGT or O-GlcNAcase revealed an inverse correlation between O-GlcNAcmodification and Ser473 phosphorylation of Akt1. MALDI-TOF/TOFmass spectrometry analysis of Akt1 immunoprecipitates fromglucosamine-treated cells, but not untreated controls, showed a peptide containing S473/T479 that was presumably modified withO-GlcNAc. Furthermore, in vitroO-GlcNAc-modification analysis of wildtype and mutant Akt1 revealed that S473 was targeted by recombinant OGT. A S473A Akt1 mutant demonstrated reduced basal and glucosamine-induced Akt1 O-GlcNAc modification compared with wildtype Akt1. Furthermore, wildtype Akt1, but not the S473A mutant, appeared to be associated with OGT following glucosamine treatment. Together, these observations suggest that Akt1 Ser473 may undergo both phosphorylation and O-GlcNAc modification, and the balance between these may regulatemurine β-pancreatic cell fate.
ISSN
0014-4827
Language
English
URI
http://www.elsevier.com/locate/yexcr
http://hdl.handle.net/10371/3239
DOI
https://doi.org/10.1016/j.yexcr.2008.04.014
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Journal Papers (저널논문_의학과)
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