The basal subcellular distribution of β‐adrenergic receptor kinase is independent of G‐protein βγ subunits

FEBS Letters

Esteban, Nuria¹  Murga, Cristina¹  Mayor, Federico¹  Ruiz-Gómez, Ana¹ 

[1] Departamento de Biologı́a Molecular and Centro de Biologı́a Molecular ‘Severo Ochoa’ (CSIC-UAM), Universidad Autónoma de Madrid, 28049-Madrid, Spain

关键词: G-protein-coupled receptor kinase;    G-protein-coupled receptor;    β-adrenergic receptor kinase;    Isoprenylation;    Kinase anchor;    G-protein;    GPCR;    G-protein-coupled receptor(s);    βARK;    β-adrenergic receptor kinase;    G-protein;    guanine nucleotide-binding protein;    GRK;    G-protein-coupled receptor kinase;    Gβ;    G-protein β subunit(s);    Gγ;    G-protein γ subunit(s);    SDS-PAGE;    sodium dodecyl sulfate–polyacrylamide gel electrophoresis;   

DOI  :  10.1016/S0014-5793(97)00476-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

β-adrenergic receptor kinase (βARK-1 or GRK2) is a key regulatory protein involved in the regulation of G-protein-coupled receptors which associates with microsomal and plasma membranes. βγ subunits of G-proteins have been suggested to mediate agonist-dependent membrane translocation of βARK, but their possible role in maintaining the complex subcellular distribution of the kinase is not known. In this study we show that lovastatin-mediated inhibition of Gγ subunits isoprenylation in HEK-293 cells stably transfected with βARK1 leads to a significant release of Gβ subunits to the cytosol without causing changes in total particulate βARK or in the association of this kinase to plasma or microsomal membrane fractions. In addition, transient overexpression of mutant forms of Gγ unable to become isoprenylated resulted in a marked sequestration of Gβ to the soluble compartment, but caused no rearrangement in the distribution of cotransfected βARK. These results indicate that anchoring of βARK to cellular membranes under basal conditions is independent of the availability of heterotrimeric G-protein subunits.

【 授权许可】

Unknown