The Downstream Regulation of Chemokine Receptor Signalling: Implications for Atherosclerosis

Figure 1

Schematic summary of chemokine-mediated GPCR signalling. Chemokine binding to the receptor induces conformational changes in its transmembrane domain to allow it to couple to a heterotrimeric G-protein. Chemokine receptors predominantly couple to Gαi proteins (green) but also Gαq proteins (purple). Chemokines also interact with their receptors to induce the formation of receptor dimers or oligomers. This induces GDP to GTP exchange at the nucleotide binding site of the Gα subunit. This causes the dissociation of the GTP-bound Gα subunit from the Gβ γ heterodimers and the activation of downstream signalling effectors. This leads to the production of second messengers which further propagate signal transduction pathways that cause a cellular response. Inactivation of the G-protein occurs through hydrolysis of GTP, allowing the Gα-GDP to recombine with the β γ dimers.