Rat Beta-arrestin-2(ARRB2) ELISA kit

Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta-arrestins bind to the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G-protein; the binding appears to require additional receptor determinants exposed only in the active receptor conformation. The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin-associated sorting proteins) and recruiting the GPRCs to the adapter protein 2 complex 2 (AP-2) in clathrin-coated pits (CCPs). However, the extent of beta-arrestin involvement appears to vary significantly depending on the receptor, agonist and cell type. Internalized arrestin-receptor complexes traffic to intracellular endosomes, where they remain uncoupled from G-proteins. Two different modes of arrestin-mediated internalization occur. Class A receptors, like ADRB2, OPRM1, ENDRA, D1AR and ADRA1B dissociate from beta-arrestin at or near the plasma membrane and undergo rapid recycling. Class B receptors, like AVPR2, AGTR1, NTSR1, TRHR and TACR1 internalize as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptors, for extended periods of time. Receptor resensitization then requires that receptor-bound arrestin is removed so that the receptor can be dephosphorylated and returned to the plasma membrane. Mediates endocytosis of CCR7 following ligation of CCL19 but not CCL21. Involved in internalization of P2RY1, P2RY4, P2RY6 and P2RY11 and ATP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of OPRD1 and subsequent recycling or degradation. Involved in ubiquitination of IGF1R. Beta-arrestins function as multivalent adapter proteins that can switch the GPCR from a G-protein signaling mode that transmits short-lived signals from the plasma membrane via small molecule second messengers and ion channels to a beta-arrestin signaling mode that transmits a distinct set of signals that are initiated as the receptor internalizes and transits the intracellular compartment. Acts as signaling scaffold for MAPK pathways such as MAPK1/3 (ERK1/2) and MAPK10 (JNK3). ERK1/2 and JNK3 activated by the beta-arrestin scaffold are largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Acts as signaling scaffold for the AKT1 pathway. GPCRs for which the beta-arrestin-mediated signaling relies on both ARRB1 and ARRB2 (codependent regulation) include ADRB2, F2RL1 and PTH1R. For some GPCRs the beta-arrestin-mediated signaling relies on either ARRB1 or ARRB2 and is inhibited by the other respective beta-arrestin form (reciprocal regulation). Increases ERK1/2 signaling in AGTR1- and AVPR2-mediated activation (reciprocal regulation). Involved in CCR7-mediated ERK1/2 signaling involving ligand CCL19. Is involved in type-1A angiotensin II receptor/AGTR1-mediated ERK activity. Is involved in type-1A angiotensin II receptor/AGTR1-mediated MAPK10 activity. Is involved in dopamine-stimulated AKT1 activity in the striatum by disrupting the association of AKT1 with its negative regulator PP2A. Involved in AGTR1-mediated chemotaxis. Appears to function as signaling scaffold involved in regulation of MIP-1-beta-stimulated CCR5-dependent chemotaxis. Involved in attenuation of NF-kappa-B-dependent transcription in response to GPCR or cytokine stimulation by interacting with and stabilizing CHUK. Suppresses UV-induced NF-kappa-B-dependent activation by interacting with CHUK. The function is promoted by stimulation of ADRB2 and dephosphorylation of ARRB2. Involved in IL8-mediated granule release in neutrophils. Involved in p53/TP53-mediated apoptosis by regulating MDM2 and reducing the MDM2-mediated degradation of p53/TP53. May serve as nuclear messenger for GPCRs. Upon stimulation of OR1D2, may be involved in regulation of gene expression during the early processes of fertilization. Also involved in regulation of receptors other than GPCRs. Involved in endocytosis of TGFBR2 and TGFBR3 and down-regulates TGF-beta signaling such as NF-kappa-B activation. Involved in endocytosis of low-density lipoprotein receptor/LDLR. Involved in endocytosis of smoothened homolog/Smo, which also requires GRK2. Involved in endocytosis of SLC9A5. Involved in endocytosis of ENG and subsequent TGF-beta-mediated ERK activation and migration of epithelial cells. Involved in Toll-like receptor and IL-1 receptor signaling through the interaction with TRAF6 which prevents TRAF6 autoubiquitination and oligomerization required for activation of NF-kappa-B and JUN. Involved in insulin resistance by acting as insulin-induced signaling scaffold for SRC, AKT1 and INSR. Involved in regulation of inhibitory signaling of natural killer cells by recruiting PTPN6 and PTPN11 to KIR2DL1. Involved in the internalization of the atypical chemokine receptor ACKR3. Acts as an adapter protein coupling FFAR4 receptor to specific downstream signaling pathways, as well as mediating receptor endocytosis. During the activation step of NLRP3 inflammasome, directly associates with NLRP3 leading to inhibition of proinflammatory cytokine release and inhibition of inflammation.

1. Arrb2 induces cardiomyocyte death by interacting with the p85 subunit of PI3K, and negatively regulating the formation of p85-PI3K/CaV3 survival complex, thus blocking activation of PI3K-Akt-GSK3beta cell survival signalling pathway in cardiac ischemia-reperfusion. PMID: 29016703
2. miR-365 targets Arrb2 to reverse morphine tolerance in rats. PMID: 27922111
3. The results of this study showed the beta-arrestin2-dependent prevalence of dopamine D1 receptor signaling in response to acute morphine or sucrose consumption elicited by food deprivation in rats. PMID: 28391016
4. GSK-3beta regulate palmitic acid-induced cardiomyocyte apoptosis by affecting the distribution of beta-Arr2 from nucleus to cytoplasm. PMID: 27431999
5. Data reveal essential roles of beta-arrestin 2 and PDE4D in a common mechanism for heterologous desensitization of cardiac beta adrenergic receptors under hormonal stimulation, which is associated with impaired cardiac function during the development of pathophysiological conditions. PMID: 28339772
6. beta-arrestin-2 has a crucial role in irisin induced glucose metabolism in T2 diabetes mellitus by regulating the p38 MAPK signaling. PMID: 28888936
7. AT1R-beta-arrestin-2 pathway signaling plays an important role in renal fibrosis. PMID: 28274926
8. Heterodimerization of the kappa opioid receptor and neurotensin receptor 1 contributes to a novel beta-arrestin-2-signaling pathway. PMID: 27523794
9. The ratio of GRK6/ARRB2 in DSP model rats was significantly higher than that in controls. PMID: 26174132
10. tryptase may directly damage IEC6 cells via PAR-2 and the downstream activation of ERK, and demonstrate that the signaling pathway requires beta-arrestin-2. PMID: 26398586
11. PKCbetaII inhibits the ubiquitination of beta-arrestin2 in an autophosphorylation-dependent manner PMID: 26545496
12. information about ligand-receptor conformation is encoded within the population average beta-arrestin2 conformation, and provide insight into how different G-protein-coupled receptors can use a common effector for different purposes PMID: 27007854
13. GPR40 functions via both G protein-mediated and beta-arrestin-mediated mechanisms; endogenous and synthetic ligands differentially engage these pathways to promote insulin secretion. PMID: 26157145
14. Arrestin 2 expression is increased in resistance arteries during early hypertension. PMID: 25972452
15. Effect of carvedilol on cardiac dysfunction 4 days after myocardial infarction in rats: role of toll-like receptor 4 and beta-arrestin 2 PMID: 23884833
16. Beta-arrestin2 is involved in the increase of distal colonic contraction in diabetic rats. PMID: 23816471
17. Platelet activating factor enhances MMP-2 production in vascular smooth muscle cells via a beta-arrestin2-dependent ERK signaling pathway. PMID: 23911909
18. Selective activation of beta-arrestin-dependent pathways may provide advantages over conventional AT1R blockers. PMID: 23873795
19. The beta-arrestin2 depletion diminishes hepatic stellate cell ERK1/2 signaling and proliferation. PMID: 23192415
20. beta-arrestin recruitment activates the NF-kappaB pathway in cultured vascular smooth muscle cells. PMID: 23576578
21. phosphorylation controls the association of TRPV1 with beta-arrestin-2. PMID: 23360390
22. metoprolol is a biased ligand that selectively activates a G protein-independent and GRK5/beta-arrestin2-dependent pathway, and induces cardiac fibrosis. PMID: 22888001
23. reduced expression by graft monocytes during acute kidney allograft rejection PMID: 21193245
24. Arrestin2 is the major arrestin subtype in the rat brain, although arrestin3 is expressed in specific cell populations. The response of receptors to specific drugs stimulating or blocking them may depend on complement of arrestins in their target cells. PMID: 11823056
25. arrestin 2 has a role in activating a MAPK pathway that regulates Nur77, which in turn modulates NK(1)R-mediated nonapoptotic programmed cell death PMID: 14769794
26. there are conformational changes associated with the transition of beta-arrestin 2 from its basal inactive conformation to its biologically active conformation PMID: 15501822
27. beta-arrestin2 utilizes mu-adaptin as an endocytic partner PMID: 17456469
28. Beta-arrestin 2 modulates acute responses to ethanol and is an important mediator of ethanol reward. PMID: 18367649
29. {beta}-Arrestin-2 Mediates Anti-apoptotic Signaling through Regulation of BAD Phosphorylation. PMID: 19171933
30. NHERF1 inhibited beta-arrestin2 binding to wtPTH1R but had no effect on beta-arrestin2 association with pdPTH1R. Such an effect may protect against PTH resistance or PTH1R down-regulation in cells harboring NHERF1. PMID: 19188335
31. Independent beta-arrestin2 and Gq/protein kinase Czeta pathways for ERK stimulated by angiotensin type 1A receptors in vascular smooth muscle cells converge on transactivation of the epidermal growth factor receptor. PMID: 19254952
32. Membrane-recruited Arrb2 is needed for beta-intergrin-mediated shear-stress-resistant leukocyte adhesion. Both Arrb 1 & 2 are needed for rapid keratinocyte-derived chemokine-induced arrest on VCAM-1, adhesion strengthening under shear requires only Arrb2. PMID: 19429870
33. Endosomal endothelin-converting enzyme-1 is a regulator of beta-arrestin-dependent ERK signaling PMID: 19531493
34. elevated Arrb2 expression in striatum and hippocampus of ethanol-preferring AA rats was associated with allelic variation (7-marker haplotype), which segregated fully between AA and ethanol-avoiding ANA lines. PMID: 18367649

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Cytoplasm. Nucleus. Cell membrane. Membrane, clathrin-coated pit. Cytoplasmic vesicle. Note=Translocates to the plasma membrane and colocalizes with antagonist-stimulated GPCRs.

Arrestin family

Predominantly localized in neuronal tissues and in the spleen.

KEGG: rno:25388

STRING: 10116.ENSRNOP00000026207

UniGene: Rn.32973