To examine the signaling pathways active downstream ACKR2, both in constitutive and ligand-stimulated conditions, we carried out a large-scale mass spec-based quantitative phosphoproteomic analysis by SILAC technique. ACKR2 has been expressed in HEK293T cells using a tetracycline-inducible system and stimulated with the common ligand CCL3L1. Using computational approaches, we performed a comparative system-based analysis of the ACKR2- and CCR5-mediated phosphoproteomes.