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Akt1 is dynamically modified with O-GlcNAc following treatments with PUGNAc and insulin-like growth factor-1

Johanna C Gandy1, Abigail E Rountree, Gautam N Bijur

  • 1Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Sparks Center, Room 1009, Birmingham, AL 35294-0017, USA.

FEBS Letters
|May 11, 2006
PubMed

Insights

The serine/threonine kinase Akt1 is modified with O-GlcNAc and can be simultaneously phosphorylated. O-GlcNAc modification of Akt1 may influence its nuclear localization.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Biochemistry

Background:

  • The Ser/Thr kinase Akt1 plays a crucial role in cellular signaling pathways, typically activated by growth factors through phosphorylation at Thr308 and Ser473.
  • O-GlcNAcylation is a dynamic post-translational modification that regulates protein function, similar to phosphorylation.

Purpose of the Study:

  • To investigate the interplay between Akt1 phosphorylation and O-GlcNAcylation.
  • To determine the effect of inhibiting O-GlcNAc removal on Akt1 modification and localization.

Main Methods:

  • Utilized SH-SY5Y cells for experiments.
  • Employed PUGNAc (O-GlcNAc inhibitor) and IGF-1 (growth factor) treatments.
  • Assessed Akt1 phosphorylation and O-GlcNAc modification levels.
  • Monitored Akt1 subcellular localization.

Main Results:

  • Akt1 was found to be constitutively modified with O-GlcNAc.
  • Inhibition of O-GlcNAc removal (PUGNAc) increased cytosolic O-GlcNAc-Akt1 levels.
  • Insulin-like growth factor-1 (IGF-1) increased both O-GlcNAc-Akt1 levels and Akt1 phosphorylation.
  • PUGNAc treatment did not inhibit IGF-1-induced Akt1 phosphorylation.
  • PUGNAc treatment led to the nuclear accumulation of Akt1.

Conclusions:

  • Akt1 can be simultaneously modified by O-GlcNAcylation and phosphorylation.
  • O-GlcNAc modification of Akt1 may regulate its nuclear localization, suggesting a novel regulatory mechanism for Akt1 activity.

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