chemokine (C-C motif) ligand 2 binding

Definition

Target type: molecularfunction

Binding to chemokine (C-C motif) ligand 2. [GOC:BHF]

Chemokine (C-C motif) ligand 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1), is a small cytokine that plays a critical role in the recruitment and activation of immune cells, particularly monocytes and macrophages, to sites of inflammation and tissue injury. Its molecular function involves a complex interplay of binding events and signaling cascades:

1. **Binding to CCR2 Receptor:** CCL2 exerts its effects by binding to its cognate receptor, chemokine receptor 2 (CCR2), which is expressed on the surface of various immune cells. This binding event initiates a signaling cascade within the target cell.

2. **G Protein Coupling and Activation:** CCR2 is a G protein-coupled receptor (GPCR). Upon CCL2 binding, the receptor undergoes conformational changes that activate a heterotrimeric G protein associated with it. This activation involves the dissociation of the G protein into its alpha, beta, and gamma subunits.

3. **Downstream Signaling Pathways:** The activated G protein subunit initiates a cascade of intracellular signaling events. The most prominent pathway involves the activation of phospholipase C (PLC), an enzyme that hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into diacylglycerol (DAG) and inositol trisphosphate (IP3).

4. **Calcium Release and Cell Migration:** IP3 triggers the release of calcium ions (Ca2+) from intracellular stores, leading to an increase in cytosolic calcium concentration. This calcium influx is crucial for various cellular processes, including cell migration.

5. **Activation of MAP Kinase Pathways:** DAG activates protein kinase C (PKC), which in turn activates mitogen-activated protein kinases (MAPKs) such as ERK, JNK, and p38. These kinases are involved in regulating gene expression, cell survival, and cell proliferation.

6. **Cell Adhesion and Chemotaxis:** CCL2 binding to CCR2 triggers the expression of adhesion molecules on the cell surface, promoting the adhesion of immune cells to the endothelium of blood vessels. This adhesion is followed by chemotaxis, the directed movement of cells along a chemical gradient, which is guided by CCL2 concentration.

7. **Immune Cell Recruitment and Activation:** Through these signaling events, CCL2 orchestrates the recruitment and activation of monocytes, macrophages, and other immune cells to sites of inflammation. These cells contribute to the inflammatory response by releasing pro-inflammatory mediators, phagocytosing pathogens and cellular debris, and presenting antigens to T cells.

In summary, CCL2 binding to CCR2 triggers a complex signaling cascade that leads to the recruitment and activation of immune cells, playing a central role in inflammatory responses, tissue repair, and immune homeostasis.'
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Proteins (1)

Compounds (19)