{Reference Type}: Journal Article
{Title}: Chemokine N-terminal-derived peptides differentially regulate signaling by the receptors CCR1 and CCR5.
{Author}: Larsen O;Schuermans S;Walser A;Louka S;Lillethorup IA;Våbenø J;Qvortrup K;Proost P;Rosenkilde MM;
{Journal}: FEBS Lett
{Volume}: 597
{Issue}: 24
{Year}: 2023 12 23
{Factor}: 3.864
{DOI}: 10.1002/1873-3468.14778
{Abstract}: Inflammatory chemokines are often elevated in disease settings, where the largest group of CC-chemokines are the macrophage inflammatory proteins (MIP), which are promiscuous for the receptors CCR1 and CCR5. MIP chemokines, such as CCL3 and CCL5 are processed at the N terminus, which influences signaling in a highly diverse manner. Here, we investigate the signaling capacity of peptides corresponding to truncated N termini. These 3-10-residue peptides displayed weak potency but, surprisingly, retained their signaling on CCR1. In contrast, none of the peptides generated a signal on CCR5, but a CCL3-derived tetrapeptide was a positive modulator boosting the signal of several chemokine variants on CCR5. In conclusion, chemokine N termini can be mimicked to produce small CCR1-selective agonists, as well as CCR5-selective modulators.