CCR2 chemokine receptor binding

Definition

Target type: molecularfunction

Binding to a CCR2 chemokine receptor. [GOC:mah, GOC:nln]

CCR2, a member of the G protein-coupled receptor (GPCR) family, plays a critical role in mediating the inflammatory response by binding to its ligands, the chemokines CCL2 (MCP-1), CCL7 (MCP-3), CCL8 (MCP-2), and CCL13 (MCP-4). Upon binding, CCR2 activates intracellular signaling cascades, primarily involving the Gαi protein, leading to downstream effects like cytoskeletal rearrangements, chemotaxis, and leukocyte activation. The molecular function of CCR2 chemokine receptor binding involves the following steps:
1. Ligand Binding: The chemokine ligand binds to the extracellular domain of CCR2, specifically to the N-terminal region and the first extracellular loop. This binding event induces conformational changes in the receptor.
2. G Protein Coupling: The conformational changes in CCR2 trigger the recruitment and activation of the Gαi protein. This protein is a heterotrimeric complex consisting of Gα, Gβ, and Gγ subunits.
3. Signaling Cascade Initiation: Activated Gαi protein dissociates from the Gβγ dimer and interacts with downstream signaling molecules, such as phospholipase C (PLC).
4. Second Messenger Production: PLC hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into diacylglycerol (DAG) and inositol triphosphate (IP3). DAG activates protein kinase C (PKC), while IP3 increases intracellular calcium levels.
5. Cellular Responses: The activation of these signaling pathways ultimately leads to a series of cellular responses, including:
- Chemotaxis: CCR2 binding to its ligands induces directional migration of leukocytes towards the source of the chemokine.
- Cytoskeletal Rearrangements: CCR2 activation leads to reorganization of the actin cytoskeleton, which is essential for cell movement and adhesion.
- Leukocyte Activation: CCR2 signaling promotes leukocyte activation, resulting in the release of inflammatory mediators and the upregulation of surface receptors involved in immune responses.
6. Receptor Desensitization: Prolonged activation of CCR2 leads to receptor desensitization, a process that limits excessive signaling. This involves the phosphorylation of the receptor by G protein-coupled receptor kinases (GRKs), followed by the binding of β-arrestin, which uncouples the receptor from the signaling cascade.
In summary, CCR2 chemokine receptor binding initiates a complex signaling cascade involving G protein coupling, second messenger production, and the activation of downstream signaling molecules, culminating in chemotaxis, cytoskeletal rearrangements, and leukocyte activation.'
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Proteins (2)

Compounds (21)