Arrestins: multifunctional regulators of signaling pathways

Abstract

The four vertebrate arrestins comprise a family of proteins that are responsible for the desensitization and internalization of over 800 subtypes of G protein-coupled receptors (GPCRs). The arrestins also serve as independent signal transducers in both a receptor-dependent and receptor-independent fashion. The nonvisual arrestins (arrestin-2 and arrestin-3, or β-arrestin-1 and β-arrestin-2) have been shown to interact with >100 signaling and trafficking proteins. In particular, the arrestins are well-characterized for their role in the scaffolding of several mitogen-activated protein kinase (MAPK) cascades. Over the course of my thesis work, I investigated the mechanisms underlying arrestin-mediated scaffolding and activation of these cascades with a specific focus on the JNK3 and ERK2 cascades.