84-5705-76　ARRB1 50ug　555595

特徴

• 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.
• Involved in internalization of P2RY4 and UTP-stimulated internalization of P2RY2.
• Involved in phosphorylation-dependent internalization of OPRD1 ands subsequent recycling.
• Involved in the degradation of cAMP by recruiting cAMP phosphodiesterases to ligand-activated receptors.
• 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).
• ERK1/2 activated by the beta-arrestin scaffold is largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes.
• Recruits c-Src/SRC to ADRB2 resulting in ERK activation.
• 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).
• Inhibits ERK1/2 signaling in AGTR1- and AVPR2-mediated activation (reciprocal regulation).
• Is required for SP-stimulated endocytosis of NK1R and recruits c-Src/SRC to internalized NK1R resulting in ERK1/2 activation, which is required for the antiapoptotic effects of SP.
• Is involved in proteinase-activated F2RL1-mediated ERK activity.
• Acts as signaling scaffold for the AKT1 pathway.
• Is involved in alpha-thrombin-stimulated AKT1 signaling.
• Is involved in IGF1-stimulated AKT1 signaling leading to increased protection from apoptosis.
• Involved in activation of the p38 MAPK signaling pathway and in actin bundle formation.
• Involved in F2RL1-mediated cytoskeletal rearrangement and chemotaxis.
• Involved in AGTR1-mediated stress fiber formation by acting together with GNAQ to activate RHOA.
• 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.
• May serve as nuclear messenger for GPCRs.
• Involved in OPRD1-stimulated transcriptional regulation by translocating to CDKN1B and FOS promoter regions and recruiting EP300 resulting in acetylation of histone H4.
• Involved in regulation of LEF1 transcriptional activity via interaction with DVL1 and/or DVL2 Also involved in regulation of receptors other than GPCRs.
• 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.
• Binds phosphoinositides.
• Binds inositolhexakisphosphate (InsP6) (By similarity).
• Involved in IL8-mediated granule release in neutrophils.
• Required for atypical chemokine receptor ACKR2-induced RAC1-LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation.
• Involved in the internalization of the atypical chemokine receptor ACKR3.
• Negatively regulates the NOTCH signaling pathway by mediating the ubiquitination and degradation of NOTCH1 by ITCH.
• Participates to the recruitment of the ubiquitin-protein ligase to the receptor
• Applications:Suitable for use in ELISA, Western Blot, Immunohistochemistry and Immunofluorescence.
• Other applications not tested.
• Recommended Dilution:Western Blot: 1:500-1:5000Immunohistochemistry: 1:200-1:500Immunofluorescence: 1:200-1:500Optimal dilutions to be determined by the researcher.
• Storage and Stability:May be stored at 4°C for short-term only.
• Aliquot to avoid repeated freezing and thawing.
• Store at -20°C.
• Aliquots are stable for 12 months after receipt.
• For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.