Beta-arrestins: Traffic cops of cell signaling

Howard Hughes Medical Institute, Duke University Medical Center, DUMC Box 3821, Durham, NC 27710, USA.
Current Opinion in Cell Biology (Impact Factor: 8.47). 05/2004; 16(2):162-8. DOI: 10.1016/
Source: PubMed


Once thought to function only in the desensitization of seven membrane spanning receptors (7MSRs), the ubiquitous beta-arrestin molecules are increasingly appreciated to play important roles in the endocytosis and signaling of these receptors. These functions reflect the ability of the beta-arrestins to bind an ever-growing list of signaling and endocytic elements, often in an agonist-dependent fashion. One heavily studied system is that leading to MAP kinase activation via beta-arrestin-mediated scaffolding of these pathways in a receptor-dependent fashion. The beta-arrestins are also found to be involved in the regulation of novel receptor systems, such as Frizzled and TGFbeta receptors.

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    • "Role of b-Arrestin 2 in GRK2-Mediated Endothelial Derangement. It is well established that b-arrestins, whose recruitment is mediated by GRKs, can act as scaffold molecules that bring different signaling molecules into a receptor complex (Lefkowitz and Whalen, 2004; DeWire et al., 2007; Premont and Gainetdinov, 2007). Our Western blotting analysis showed that HUVECs constitutively expressed b-arrestin 2 (see Figs. 5B and 6). "
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    • "In the fi rst 5 min of spontaneous activity in the open fi eld arena, fl ies show intensive exploration of a novel environment , with crucial role of Kurtz nonvisual arrestin in the nervous system (Liu et al. 2007). Th e krz gene encodes the only nonvisual arrestin in Drosophila (Roman et al. 2000) which is important scaff olding proteins regulating the activity of several families of cell-surface receptors (Lefkowitz and Whalen 2004). In later phase of fl ies ' activity in the open fi eld arena dopamine takes place (Bainton et al. 2000, Friggi-Grelin et al. 2003). "
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    • "However, β-arrestins are also essential for endocytosis of receptors via clathrin-coated pits through interactions with clathrin [22] and AP-2 adaptor protein [23]. More recently, it has been shown that β-arrestins coordinate several G protein-independent GPCR signaling cascades [24]–[26]. In these cases, the β-arrestin typically serves as a molecular scaffold, assembling multiple elements of a signaling cascade at activated receptors, thereby regulating the temporal and spatial activity of the pathway. "
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