FIGURE 8.

Schematic representation of the mechanism by which C5L2 negatively modulates C5a-C5aR-mediated ERK1/2 activation in human neutrophils. C5L2 functions as an intracellular receptor, becoming activated only after ligand binding to the C5aR. Receptor activation induces phosphorylation by G protein receptor kinases (GRK), facilitating their association with β-arrestin. The C5aR-β-arrestin complex activates ERK1/2, whereas the C5L2-β-arrestin complex inhibits ERK1/2, and the net signal is a result of the balance of the two.