This study investigates the role of β-arrestins in the activation and targeting of extracellular signal-regulated kinase 2 (ERK2) following stimulation of angiotensin II type 1a receptors (AT1aR). Using confocal immunofluorescence microscopy and biochemical approaches, the researchers found that angiotensin II stimulation triggers β-arrestin-2 binding to the receptor and internalization of AT1aR-β-arrestin complexes. ERK2 redistribution into endosomal vesicles containing the internalized AT1aR-β-arrestin complexes was observed, indicating the formation of multi-protein complexes containing AT1aR, β-arrestin-2, and component kinases of the ERK cascade. β-Arrestin-2 was found to facilitate the assembly of a cRaf-1, MEK1, ERK2 complex, and the phosphorylation of ERK2 in β-arrestin complexes was significantly enhanced by coexpression of cRaf-1. These findings suggest that β-arrestins function as scaffolds to enhance cRaf-1 and MEK-dependent activation of ERK2 and as targeting proteins that direct activated ERK to specific subcellular locations. The study also highlights the role of β-arrestins in heptahelical receptor signaling, beyond their traditional role in uncoupling G proteins and targeting receptors for endocytosis. β-Arrestins can directly interact with component kinases of the ERK and JNK MAPK cascades, facilitating their activation. The results indicate that β-arrestins are multifunctional adapter proteins that link heptahelical receptors to a defined subset of effector enzymes. The study provides insights into the complex mechanisms by which β-arrestins regulate MAPK signaling and contribute to cellular responses.This study investigates the role of β-arrestins in the activation and targeting of extracellular signal-regulated kinase 2 (ERK2) following stimulation of angiotensin II type 1a receptors (AT1aR). Using confocal immunofluorescence microscopy and biochemical approaches, the researchers found that angiotensin II stimulation triggers β-arrestin-2 binding to the receptor and internalization of AT1aR-β-arrestin complexes. ERK2 redistribution into endosomal vesicles containing the internalized AT1aR-β-arrestin complexes was observed, indicating the formation of multi-protein complexes containing AT1aR, β-arrestin-2, and component kinases of the ERK cascade. β-Arrestin-2 was found to facilitate the assembly of a cRaf-1, MEK1, ERK2 complex, and the phosphorylation of ERK2 in β-arrestin complexes was significantly enhanced by coexpression of cRaf-1. These findings suggest that β-arrestins function as scaffolds to enhance cRaf-1 and MEK-dependent activation of ERK2 and as targeting proteins that direct activated ERK to specific subcellular locations. The study also highlights the role of β-arrestins in heptahelical receptor signaling, beyond their traditional role in uncoupling G proteins and targeting receptors for endocytosis. β-Arrestins can directly interact with component kinases of the ERK and JNK MAPK cascades, facilitating their activation. The results indicate that β-arrestins are multifunctional adapter proteins that link heptahelical receptors to a defined subset of effector enzymes. The study provides insights into the complex mechanisms by which β-arrestins regulate MAPK signaling and contribute to cellular responses.