Phospho-β-Arrestin 1 (Ser412) (6-24) Mouse mAb #2416

Arrestin proteins function as negative regulators of G protein-coupled receptor (GPCR) signaling. Cognate ligand binding stimulates GPCR phosphorylation, which is followed by binding of arrestin to the phosphorylated GPCR and the eventual internalization of the receptor and desensitization of GPCR signaling (1). Four distinct mammalian arrestin proteins are known. Arrestin 1 (also known as S-arrestin) and arrestin 4 (X-arrestin) are localized to retinal rods and cones, respectively. Arrestin 2 (also known as β-arrestin 1) and arrestin 3 (β-arrestin 2) are ubiquitously expressed and bind to most GPCRs (2). β-arrestins function as adaptor and scaffold proteins and play important roles in other processes, such as recruiting c-Src family proteins to GPCRs in Erk activation pathways (3,4). β-arrestins are also involved in some receptor tyrosine kinase signaling pathways (5-8). Additional evidence suggests that β-arrestins translocate to the nucleus and help regulate transcription by binding transcriptional cofactors (9,10).
Erk1/2 constitutively phosphorylates β-arrestin 1 at carboxy-terminal Ser412, which promotes cytosolic localization of the scaffold protein (11). Agonist stimulation of β2-adrenergic receptors results in recruitment of β-arrestin 1 to the plasma membrane and rapid dephosphorylation of arrestin. Dephosphorylation is an essential step of β-arrestin 1-mediated receptor endocytosis, but it is not required for receptor desensitization (12).