Reactome: A Curated Pathway Database


Stable Identifier
Homo sapiens
Locations in the PathwayBrowser

Beta arrestins 1 and 2 are required for the endocytosis and downregulation of numerous GPCRs including ADRB2, CHRM2, FZD, C5aR and many others (Ferguson et al, 1995; Goodman et al, 1995; Chen et al, 2003; Gurevich et al, 1995; Braun et al, 2003; reviewed in Kovacs et al, 2009; Traub and Bonifacino, 2013). Beta-arrestin mediated downregulation of GPCRs is modulated by receptor phosphorylation status (see for instance Fessart et al, 2007; Braun et al, 2003; reviewed in Gurevich and Gurevich, 2006). In addition to recognizing GPCR cargo, beta-arrestins also bind directly to the AP-2 complex, thus mediating the recruitment of cargo into nascent clathrin coated vesicles (Edeling et al, 2006; Schmid et al, 2006; reviewed in Traub and Bonifacino, 2013; Kang et al, 2014). A recent study has shown that in addition to mediating GPCR endocytosis, beta-arrestin2 can be recruited to CCPs after dissociation from ADRB2 to promote MAPK signaling, highlighting a role for CCPs as signaling microdomains (Eichel et al, 2016).

Literature References
PubMed ID Title Journal Year
12958364 Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4 Science 2003
8553074 Role of beta-arrestin in mediating agonist-promoted G protein-coupled receptor internalization Science 1996
24680432 Role of ?-arrestins and arrestin domain-containing proteins in G protein-coupled receptor trafficking Curr. Opin. Cell Biol. 2014
16460808 The structural basis of arrestin-mediated regulation of G-protein-coupled receptors Pharmacol. Ther. 2006
8837779 Beta-arrestin acts as a clathrin adaptor in endocytosis of the beta2-adrenergic receptor Nature 1996
16903783 Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly PLoS Biol. 2006
26829388 ?-Arrestin drives MAP kinase signalling from clathrin-coated structures after GPCR dissociation Nat. Cell Biol. 2016
12464600 Phosphorylation of key serine residues is required for internalization of the complement 5a (C5a) anaphylatoxin receptor via a beta-arrestin, dynamin, and clathrin-dependent pathway J. Biol. Chem. 2003
16516836 Molecular switches involving the AP-2 beta2 appendage regulate endocytic cargo selection and clathrin coat assembly Dev. Cell 2006
7822302 Arrestin interactions with G protein-coupled receptors. Direct binding studies of wild type and mutant arrestins with rhodopsin, beta 2-adrenergic, and m2 muscarinic cholinergic receptors J. Biol. Chem. 1995
24186068 Cargo recognition in clathrin-mediated endocytosis Cold Spring Harb Perspect Biol 2013
17456551 Src-dependent phosphorylation of beta2-adaptin dissociates the beta-arrestin-AP-2 complex J. Cell. Sci. 2007
19853559 Arrestin development: emerging roles for beta-arrestins in developmental signaling pathways Dev. Cell 2009
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