ACKR2 Protein, Human (Cell-Free, His)

ACKR2, an atypical chemokine receptor, orchestrates precise control over chemokine levels and localization through high-affinity chemokine binding, operating independently of classic ligand-driven signal transduction cascades. Also referred to as an interceptor, internalizing receptor, chemokine-scavenging receptor, or chemokine decoy receptor, ACKR2 serves as a receptor for a diverse array of chemokines, including CCL2, CCL3, CCL3L1, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL17, CCL22, CCL23, CCL24, SCYA2/MCP-1, SCY3/MIP-1-alpha, SCYA5/RANTES, and SCYA7/MCP-3. Upon active ligand stimulation, it triggers a beta-arrestin 1 (ARRB1)-dependent, G protein-independent signaling pathway, leading to the phosphorylation of the actin-binding protein cofilin (CFL1) through a RAC1-PAK1-LIMK1 signaling cascade. Activation of this pathway facilitates the relocation of ACKR2 from endosomal compartments to the cell membrane, enhancing its efficiency in chemokine uptake and degradation. By scavenging chemokines in tissues, lymphatic vessel surfaces, and the placenta, ACKR2 plays a pivotal role in resolving the inflammatory response and regulating adaptive immune responses. Moreover, it acts as a key regulator of inflammatory leukocyte interactions with lymphatic endothelial cells (LECs) and is essential for discerning immature/mature dendritic cells by LECs. ACKR2 also contributes significantly to immune silencing of macrophages during inflammation resolution.