Interaction between O-GlcNAc modification and tyrosine phosphorylation of prohibitin: implication for a novel binary
Sudharsana R Ande1, Saby Moulik, Suresh Mishra
1Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Plos One
|February 25, 2009
Summary
Prohibitin (PHB) interacts with O-GlcNAc transferase (OGT) and undergoes O-GlcNAc modification and tyrosine phosphorylation. These modifications influence OGT activity and suggest a novel binary switch in cell signaling.
Area of Science:
- Cellular Biology
- Molecular Signaling
- Post-Translational Modifications
Background:
- Prohibitin (PHB) is a conserved, multifunctional protein involved in various cellular processes.
- The precise mechanisms governing PHB's functions, particularly its post-translational modifications, remain incompletely understood.
- Dynamic post-translational modifications like O-GlcNAcylation and tyrosine phosphorylation are crucial regulators of protein function and cellular signaling.
Purpose of the Study:
- To investigate the interaction between Prohibitin (PHB) and O-GlcNAc transferase (OGT).
- To elucidate the interplay between O-GlcNAc modification and tyrosine phosphorylation on PHB.
- To explore the functional consequences of these modifications on PHB and OGT activity within cellular signaling pathways.
Main Methods:
- Site-directed mutagenesis was employed to substitute key tyrosine, serine, and threonine residues in PHB.
- Analysis of O-GlcNAc modification and tyrosine phosphorylation levels in wild-type and mutant PHB proteins.
- Assessment of OGT activity in response to modifications in PHB.
- Bioinformatic analysis of known O-GlcNAc and tyrosine phosphorylated proteins to identify potential associations.
Main Results:
- Prohibitin (PHB) directly interacts with O-GlcNAc transferase (OGT) and is subject to O-GlcNAc modification and insulin-induced tyrosine phosphorylation.
- Mutagenesis of tyrosine residues (Tyr114, Tyr259) in PHB reduced its own tyrosine phosphorylation and O-GlcNAc modification, while enhancing OGT activity.
- Mutagenesis of serine (Ser121) and threonine (Thr258) residues attenuated O-GlcNAc modification and increased PHB tyrosine phosphorylation, indicating a link between these modifications.
Conclusions:
- O-GlcNAc modification and tyrosine phosphorylation of Prohibitin (PHB) are dynamically linked and influence OGT activity.
- These modifications likely play a significant role in insulin and other tyrosine kinase signaling pathways.
- The interplay between O-GlcNAc modification and tyrosine phosphorylation represents a novel binary switch mechanism in cellular signaling.
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