-arrestins-1 and 2 are known to play important roles in desensitization of membrane receptors and facilitation of signal transduction pathways. It has been previously shown that -arrestins are required for signal termination, internalization and ERK1/2 activation downstream of Protease-activated-receptor-2 (PAR-2), but it is unclear whether they are functionally redundant or mediate specific events. Here we demonstrate that in MEFs from -arrestin-1/2 knockout mice, Gq signaling by PAR-2, as measured by mobilization of intracellular Ca²⁺, is prolonged. Only expression of -arrestin-1 shortened the signal duration, whereas either -arrestin-1 or 2 was able to restore Protein Kinase C-induced receptor desensitization. -arrestin-1 also mediated early, while -arrestin-2 mediated delayed, receptor internalization and membrane-associated ERK1/2 activation. While -arrestin-1 colocalized with a lysosomal marker (LAMP-1), -arrestin-2 did not, suggesting a specific role for -arrestin-1 in lysosomal receptor degradation. Together these data suggest distinct temporal and functional roles for -arrestins in PAR-2 signaling, desensitization and internalization.