Rac1 plays a crucial role in MCP-1-induced monocyte adhesion and migration.
Cell Immunol
; 401-402: 104843, 2024.
Article
in En
| MEDLINE
| ID: mdl-38905771
ABSTRACT
Monocyte migration is an important process in inflammation and atherogenesis. Identification of the key signalling pathways that regulate monocyte migration can provide prospective targets for prophylactic treatments in inflammatory diseases. Previous research showed that the focal adhesion kinase Pyk2, Src kinase and MAP kinases play an important role in MCP-1-induced monocyte migration. In this study, we demonstrate that MCP-1 induces iPLA2 activity, which is regulated by PKCß and affects downstream activation of Rac1 and Pyk2. Rac1 interacts directly with iPLA2 and Pyk2, and plays a crucial role in MCP-1-mediated monocyte migration by modulating downstream Pyk2 and p38 MAPK activation. Furthermore, Rac1 is necessary for cell spreading and F-actin polymerization during monocyte adhesion to fibronectin. Finally, we provide evidence that Rac1 controls the secretion of inflammatory mediator vimentin from MCP-1-stimulated monocytes. Altogether, this study demonstrates that the PKCß/iPLA2/Rac1/Pyk2/p38 MAPK signalling cascade is essential for MCP-1-induced monocyte adhesion and migration.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Monocytes
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Signal Transduction
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Cell Adhesion
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Cell Movement
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Chemokine CCL2
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Rac1 GTP-Binding Protein
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P38 Mitogen-Activated Protein Kinases
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Focal Adhesion Kinase 2
Limits:
Humans
Language:
En
Year:
2024
Type:
Article