Similarities and differences in RANTES- and (AOP)-RANTES-triggered signals: Implications for chemotaxis

Chemokines are a family of proinflammatory cytokines that attract and activ ate specific types of leukocytes. Chemokines mediate their effects via inte raction with seven transmembrane G protein-coupled receptors (GPCR). Using CCR5-transfected HEK-293 cells, we show that both the CCR5 ligand, RANTES, as well as its derivative, aminooxypentane (AOP)-RANTES, trigger immediate responses such as Ca2+ influx, receptor dimerization, tyrosine phosphorylat ion, and G alpha(i) as well as JAK/STAT association to the receptor. In con trast to RANTES, (AOP)-RANTES is unable to trigger late responses, as measu red by the association of focal adhesion kinase (FAK) to the chemokine rece ptor complex, impaired cell polarization required for migration, or chemota xis. The results are discussed in the context of the dissociation of the la te signals, provoked by the chemokines required for cell migration, from ea rly signals.