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

Eun Sil Kang, Dohyun Han, Jungeun Park, Tae Kyoung Kwak, Min A. Oh, Sin Ae Lee, Suyong Choi, Zee Yong Park, Youngsoo Kim, Jung Weon Lee

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

O-GlcNAc transferase (OGT)-mediated modification of protein Ser/Thr residues with O-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-GlcNAc modification and Ser473 phosphorylation of Akt1. MALDI-TOF/TOF mass spectrometry analysis of Akt1 immunoprecipitates from glucosamine-treated cells, but not untreated controls, showed a peptide containing S473/T479 that was presumably modified with O-GlcNAc. Furthermore, in vitro O-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 regulate murine β-pancreatic cell fate.

Original languageEnglish (US)
Pages (from-to)2238-2248
Number of pages11
JournalExperimental Cell Research
Volume314
Issue number11-12
DOIs
StatePublished - 2008
Externally publishedYes

Keywords

  • Akt
  • Apoptosis
  • O-glycosylation
  • Phosphorylation
  • Posttranslational modification

ASJC Scopus subject areas

  • Cell Biology

Fingerprint

Dive into the research topics of 'O-GlcNAc modulation at Akt1 Ser473 correlates with apoptosis of murine pancreatic β cells'. Together they form a unique fingerprint.

Cite this