ARRB2
ARRB2 (arrestin beta 2, also known as beta-arrestin-2, BARR2 and ARR2) is a member of the classical arrestin family that regulates agonist-mediated G protein-coupled receptor signalling. It mediates receptor desensitisation, internalisation and resensitisation, and acts as a signalling scaffold. Browse Assay Genie's current range of ARRB2 research reagents below, or read on for the biology behind the target.
ARRB2 regulates agonist-mediated G protein-coupled receptor (GPCR) signalling. During homologous desensitisation, beta-arrestins bind the phosphorylated receptor and sterically prevent its coupling to the cognate G protein. They also act as endocytic adapters, recruiting receptors to the AP-2 complex in clathrin-coated pits and directing them to endosomes. Class A receptors such as ADRB2 and OPRM1 dissociate from beta-arrestin near the plasma membrane and recycle rapidly, whereas class B receptors such as AVPR2, AGTR1 and NTSR1 traffic with it to endosomal vesicles for extended periods.
Beta-arrestins also switch a GPCR from a G protein signalling mode to a beta-arrestin signalling mode. ARRB2 serves as a scaffold for MAPK pathways, including ERK1/2 and JNK3, which are held in cytoplasmic compartments such as endocytic vesicles, and for the AKT1 pathway. For some receptors, including ADRB2, F2RL1 and PTH1R, signalling depends on both ARRB1 and ARRB2, while for others one beta-arrestin is inhibited by the other. ARRB2 also stabilises CHUK to attenuate NF-kappa-B-dependent transcription, reduces MDM2-mediated degradation of p53, binds TRAF6 in Toll-like receptor and IL-1 receptor signalling, and associates directly with NLRP3 to inhibit inflammation.
Its roles extend beyond GPCRs to the endocytosis of TGFBR2, TGFBR3, LDLR, smoothened, endoglin and ACKR3, and to insulin-induced signalling complexes linked to insulin resistance. The ARRB2 gene encodes a member of the arrestin family and is expressed at high levels in the central nervous system, where it may regulate synaptic receptors. A cDNA was also isolated from thyroid gland, suggesting a role in TSH receptor desensitisation. Alternatively spliced transcript variants encode different isoforms. The mouse and rat orthologues are both named Arrb2.
ARRB2 binds phosphorylated receptors, blocks G protein coupling and recruits them to clathrin-coated pits, making it central to receptor internalisation studies.
As a scaffold for ERK1/2, JNK3 and AKT1, ARRB2 helps define G protein-independent signalling that begins as receptors internalise.
ARRB2 interacts with CHUK, TRAF6 and NLRP3 to limit NF-kappa-B activation and inflammasome-driven cytokine release.
ARRB2 is highly expressed in the central nervous system, mediates dopamine-stimulated AKT1 activity in the striatum and is implicated in insulin resistance.
ARRB2 regulates GPCR signalling by binding activated, phosphorylated receptors, blocking G protein coupling and acting as an endocytic adapter that recruits receptors to clathrin-coated pits. It also scaffolds signalling complexes for ERK1/2, JNK3 and AKT1, and modulates NF-kappa-B and p53 pathways.
ARRB2 stands for arrestin beta 2, previously named arrestin, beta 2. UniProt calls the protein beta-arrestin-2, and aliases include BARR2, ARR2 and DKFZp686L0365. HGNC places it in the classical arrestins group. Multiple alternatively spliced transcript variants encode different isoforms.
Mouse and rat both have an Arrb2 orthologue. ARRB2 is closely related to ARRB1; like ARRB1, it inhibits beta-adrenergic receptor function in vitro. Some GPCRs need both beta-arrestins, while others show reciprocal regulation. Check the datasheet of any product for its validated reactivity.
The closely related beta-arrestin paralogue and other targets in GPCR regulation and signalling.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P32121; product specifications from Assay Genie datasheets.