Differential consequences of CCL19 versus CCL21 ligation to C-C chemokine receptor 7. CCR7 signaling activates the mitogen-activated protein kinase signaling module leading to chemotaxis, whereas the Rho-coffilin signaling axis is involved in controlling the migratory speed of leukocytes. Ligand binding to and activation of CCR7 leads to its phosphorylation by GRKs that recruit β-arrestin scaffold proteins. Signaling by both CCL19 and CCL21 causes GRK6 to phosphorylate CCR7. In addition, GRK3 phosphorylates CCR7 after CCL19 ligation only. The differential phosphorylation pattern may recruit distinct functional pools of β-arrestins that leads to the differential ability of CCR7 ligands to induce clathrin-dependent receptor endocytosis and desensitization. After internalization, CCR7 recycles back to the plasma membrane, whereas CCL19 is sorted to lysosomes for degradation.