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Updated: May 19, 2026
09:16
Simultaneous Study of the Recruitment of Monocyte Subpopulations Under Flow In Vitro
Published on: November 26, 2018
Monocyte Migration Emerges from a Divergent Chemokine Signaling Network
Sean S So1, Alexis Lona2, Rina Pokhrel1
1Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
Biorxiv : the Preprint Server for Biology
|May 18, 2026
Summary
Chemokine receptor signaling drives cell migration through a complex network. Targeting divergent pathways within this network can block inflammation, offering new therapeutic strategies for immune diseases.
Area of Science:
- Immunology
- Cell Biology
- Systems Biology
Background:
- Leukocyte migration is crucial for immune homeostasis and inflammatory diseases.
- Chemokine receptors and their ligands regulate cell movement.
- Understanding chemokine-stimulated signal transduction is key to controlling immune responses.
Purpose of the Study:
- To map the chemokine-stimulated signal transduction network in monocytic THP-1 cells.
- To elucidate the molecular mechanisms underlying chemokine-induced cell migration.
- To identify potential targets for modulating chemokine-driven inflammation.
Main Methods:
- Global phosphoproteomics to identify changes in phosphorylated proteins.
- Network modeling using the PHONEMeS algorithm to reconstruct signaling pathways.
- Validation using kinase inhibitors to block cell migration.
Main Results:
- Identified 630 time-resolved changes in phosphorylated proteins downstream of CCR2.
- Generated a highly divergent CCR2 signaling network with multiple regulatory branches.
- Demonstrated that inhibiting specific network branches effectively blocks chemokine-stimulated cell migration.
Conclusions:
- Cellular chemotaxis emerges from an integrated response to divergent signaling pathways.
- The CCR2 signaling network is complex and multifaceted.
- Inhibiting any divergent pathway within the network may offer a strategy for pharmacological blockade of chemokine-driven inflammation.
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