2. Signaling Pathways
  3. GPCR/G Protein
  4. RGS Protein
  5. RGS8 Isoform

RGS8

RGS8 (Regulator of G-protein Signaling 8) is a member of the R4 subfamily of regulator of G-protein signaling proteins and functions as a GTPase-activating protein that accelerates GTP hydrolysis on activated Gα subunits, thereby terminating G protein-coupled receptor (GPCR) signaling cascades[1][2]. RGS8 contains a conserved RGS domain and regulates signaling downstream of multiple GPCR pathways, including muscarinic acetylcholine receptor and dopamine receptor signaling, highlighting its role in neuronal signal transduction and cellular responsiveness[2][3]. Mechanistically, RGS8 modulates GPCR-dependent signaling kinetics and can regulate downstream effectors such as G-protein-coupled inwardly rectifying potassium channels, calcium signaling pathways, and ERK-associated signaling networks[3][4]. Structural studies demonstrated that RGS8 interacts with both Gαi/o and Gαq family proteins and adopts a conserved binding mode with Gαq, providing an important framework for understanding G-protein selectivity among RGS family members[5]. In disease-relevant and experimental systems, RGS8 is highly expressed in the central nervous system, particularly in cerebellar regions, and has been associated with neuronal signaling regulation and neurobiological research models[3][6]. Compared with related isoforms such as RGS2, which exhibits distinctive Gαq selectivity, RGS8 displays broader substrate recognition within canonical R4-family signaling mechanisms, making it a useful model for studying GPCR signal termination and G-protein regulatory specificity[5]. Although RGS proteins are considered attractive pharmacological targets for modulating GPCR signaling, selective RGS8-directed agonists or inhibitors remain limited, and current applications primarily focus on mechanistic and signaling pathway investigations[7].

RGS8 Related Products (2):

Cat. No. Product Name Effect Purity
  • HY-13509
    CCG-50014
    		Inhibitor 99.62%
    CCG-50014 is the most potent against the regulator of G-protein signaling protein type 4 (RGS4) (IC50 =30 nM) and is >20-fold selective for RGS4 over other RGS proteins. CCG-50014 binds covalently to the RGS, forming an adduct on two cysteine residues located in an allosteric regulatory site. CCG50014, reduces nociceptive responses and enhances opioid-mediated analgesic effects in the mouse formalin test.
  • HY-U00431
    CCG 203769
    		Inhibitor 99.76%
    CCG 203769 is a selective G protein signaling (RGS4) inhibitor, which blocks the RGS4-Gαo protein-protein interaction in vitro with an IC50 of 17 nM.