Title : Extensive crosstalk between O-GlcNAcylation and phosphorylation regulates
Akt signaling
Abstract :
- O-linked N-acetylglucosamine glycosylations (O-GlcNAc) and O-linked phosphorylations (O-phosphate), as two important types of post-translational modifications, often occur on the same protein and bear a reciprocal relationship
- In addition to the well documented phosphorylations that control Akt activity, Akt also undergoes O-GlcNAcylation, but the interplay between these two modifications and the biological significance remain unclear, largely due to the technique challenges
- Here, we applied a two-step analytic approach composed of the O-GlcNAc immunoenrichment and subsequent O-phosphate immunodetection
- Such an easy method enabled us to visualize endogenous glycosylated and phosphorylated Akt subpopulations in parallel and observed the inhibitory effect of Akt O-GlcNAcylations on its phosphorylation
- Further studies utilizing mass spectrometry and mutagenesis approaches showed that O-GlcNAcylations at Thr 305 and Thr 312 inhibited Akt phosphorylation at Thr 308 via disrupting the interaction between Akt and PDK1
- The impaired Akt activation in turn resulted in the compromised biological functions of Akt , as evidenced by suppressed cell proliferation and migration capabilities
- Together, this study revealed an extensive crosstalk between O-GlcNAcylations and phosphorylations of Akt and demonstrated O-GlcNAcylation as a new regulatory modification for Akt signaling
Output (sent_index, trigger,
protein,
sugar,
site):
- 5. Thr, , -, O-GlcNAcylations, Thr 305 and Thr 312
- 7. Akt, , Akt, O-GlcNAcylations, -
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):
- 5. Akt, O-GlcNAcylations, Thr 305 and Thr 312