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Updated: Jun 23, 2026
07:28
JUMPn: A Streamlined Application for Protein Co-Expression Clustering and Network Analysis in Proteomics
Published on: October 19, 2021
Deciphering O‑GlcNAc-Dependent Signaling Via Integrated Proteomics and Phosphoproteomics
Ci Wu1,2, Chunyan Hou1, Xinyue Wang2
1Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia 20007, United States.
ACS Omega
|June 22, 2026
Summary
This study reveals extensive crosstalk between protein phosphorylation and O-linked N-acetylglucosamine (O-GlcNAcylation) modifications. We identified casein kinase 2 α (CK2α) as a key enzyme in regulating this glycosylation-dependent signaling.
Area of Science:
- Biochemistry
- Molecular Biology
- Cellular Signaling
Background:
- Post-translational modifications (PTMs) are vital for biological processes.
- Phosphorylation and O-GlcNAcylation are dynamic PTMs crucial for cellular function and disease.
- The crosstalk between these two modifications is increasingly recognized but poorly understood.
Purpose of the Study:
- To investigate the crosstalk between phosphorylation and O-GlcNAcylation.
- To elucidate the molecular mechanisms underlying this crosstalk in pancreatic cancer cells.
Main Methods:
- Utilized the PANC-1 cell line.
- Applied proteomic and phosphoproteomic analyses.
- Used specific inhibitors OSMI-1 and Thiamet G to modulate O-GlcNAc cycling.
- Conducted kinase inhibition experiments and in vitro kinase assays.
Main Results:
- Significant alterations in 2289 phosphosites (OSMI-1) and 2201 phosphosites (TMG) were observed, indicating extensive crosstalk.
- Widespread changes in kinome and phosphatome phosphorylation were detected after short-term inhibitor treatment.
- Phosphorylation of O-GlcNAcase (OGA) at S364 was identified to be mediated by casein kinase 2 α (CK2α).
Conclusions:
- This study uncovers significant crosstalk between phosphorylation and O-GlcNAcylation.
- Demonstrates glycosylation-dependent cellular signaling pathways.
- Identifies CK2α as a key regulator of OGA phosphorylation, providing insights into multilayered crosstalk mechanisms.
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