The role and mechanism of β-arrestin2 in signal transduction

β-arrestin2 is a ubiquitously expressed scaffold protein localized on the cytoplasm and plasma membrane. It was originally found to bind to GPCRs, uncoupling G proteins and receptors' binding and inhibiting the signal transduction of the GPCRs. Further investigations have revealed that β-arrestin2 not only mediates the desensitization of GPCRs but also serves as a multifunctional scaffold to mediate receptor internalization, kinase activation, and regulation of various signaling pathways, such as TLR4/NF-κB, MAPK, Wnt, TGF-β, and AMPK/mTOR pathways. β-arrestin2 regulates cell invasion, migration, autophagy, angiogenesis, and anti-inflammatory effects by regulating various signaling pathways, which play a vital role in many physiological and pathological processes. This paper reviews the structure and function of β-arrestin2, the regulation of β-arrestin2 based signaling pathways. The role and mechanism of β-arrestin2 signaling have been delineated in sufficient detail. The prospect of regulating the expression and activity of β-arrestin2 in multisystem diseases holds substantial therapeutic promise.