Related Experiment Video

Updated: Aug 6, 2026

Phospho Flow Cytometry with Fluorescent Cell Barcoding for Single Cell Signaling Analysis and Biomarker Discovery
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
PubMed

Insights

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.
Keywords:
CLK4RNA splicingphosphoproteomephosphosite co-regulation

More Related Videos

Navigating the Mass Spectrometry-Based Proteomic Data Using Free Computational Tools07:01

Navigating the Mass Spectrometry-Based Proteomic Data Using Free Computational Tools

Published on: August 19, 2025

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...