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Updated: Aug 6, 2026
08:38
Phospho Flow Cytometry with Fluorescent Cell Barcoding for Single Cell Signaling Analysis and Biomarker Discovery
Published on: October 4, 2018
Global Phosphoproteome Analysis Identifies CLK4 Co-Regulatory Pathways Driving Tumor-Specific Dysregulation
Apoorva Pai1, Leona Dcunha1, Athira Perunelly Gopalakrishnan1
1Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University), Mangalore, Karnataka, India.
Omics : a Journal of Integrative Biology
|July 22, 2026
Summary
Dual-specificity protein kinase CLK4 regulates mRNA splicing and DNA repair. This study maps CLK4
Area of Science:
- Molecular Biology
- Cellular Biology
- Cancer Research
Background:
- Dual-specificity protein kinase CLK4 (CLK4) is crucial for regulating alternative mRNA splicing, DNA repair, and cellular processes via phosphorylation.
- Understanding CLK4's phosphoproteomic landscape is vital for elucidating its role in cellular functions and disease, particularly cancer.
Purpose of the Study:
- To comprehensively map the CLK4 phosphoproteomic network using global human cellular phosphoproteome data.
- To identify key phosphorylation sites, co-regulated proteins, interactors, and downstream substrates of CLK4.
- To investigate the dysregulation of CLK4 phosphorylation in various human cancers.
Main Methods:
- Analysis of 3825 global human cellular phosphoproteome studies.
- Identification of high-confidence Class-1 phosphosites (localization probability ≥ 75%; A-score ≥ 13).
- Bioinformatic prediction of co-regulated proteins, binary interactors, and upstream kinases.
Main Results:
- Identified 430 qualitative profiles and 55 quantitative differential datasets, highlighting S136 and S138 as predominant CLK4 phosphorylation sites.
- Discovered co-regulated phosphoproteins (e.g., SQSTM1, SRRT, TP53BP1) and interactors (e.g., SRRM2, IWS1) linking CLK4 to RNA splicing, autophagy, and DNA damage response.
- Revealed tumor-specific dysregulation of CLK4 phosphorylation at key residues, with co-occurring alterations and somatic mutations suggesting disrupted CLK4 regulation in cancer.
Conclusions:
- This study provides a detailed phosphoproteomic map of CLK4's regulatory network.
- Identified specific CLK4 phosphorylation sites and associated proteins involved in critical cellular pathways and cancer progression.
- The findings offer a resource for mechanistic investigations into CLK4 function and the development of targeted cancer therapies.
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