(A) When a chemokine (blue, green or brown line) binds to a chemokine receptor (black lines) embedded in the plasma membrane (PM; grey) of a cell, a G protein formed of three subunits (α, ß, γ), one of which (α) is attached to a molecule called GDP, is recruited. The GDP is then replaced with a molecule known as GTP, the G protein dissociates, and the different subunits go on to activate a range of different cellular pathways. (B) Different models can explain how chemokines signal within a cell. In the first model (left), different chemokines (L1, L2, L3) bind to their corresponding receptors (R1, R2, R3) and activate a generic G protein mediated pathway (G) in two types of cells (in yellow and green). The final response (RE1, RE2) triggered by a chemokine is ultimately dependent on interpretation modules (depicted as cellular brains) that are specific to the cell type, rather than on the identity of the signaling chemokine-receptor complex. The second model (right) proposes that each chemokine-receptor pairs activates a specific cellular pathway that determines a particular cellular response. The work by Malhotra et al. supports the first model (Malhotra et al., 2018).