Logo image
Expression, purification, and characterization of the G protein-coupled receptor kinase GRK6
Journal article   Open access   Peer reviewed

Expression, purification, and characterization of the G protein-coupled receptor kinase GRK6

R P Loudon and J L Benovic
The Journal of biological chemistry, v 269(36), pp 22691-22697
09 Sep 1994
PMID: 8077221
url
https://doi.org/10.1016/S0021-9258(17)31701-5View
Published, Version of Record (VoR) Open

Abstract

Amino Acid Sequence Animals Cations, Divalent Cell Line Electrophoresis, Polyacrylamide Gel Enzyme Activation G-Protein-Coupled Receptor Kinases Gene Expression GTP-Binding Proteins - biosynthesis GTP-Binding Proteins - isolation & purification GTP-Binding Proteins - metabolism Humans Kinetics Magnesium - pharmacology Manganese - pharmacology Molecular Sequence Data Molecular Weight Moths Oligopeptides - metabolism Phosphorylation Protein-Serine-Threonine Kinases Receptor Protein-Tyrosine Kinases - biosynthesis Receptor Protein-Tyrosine Kinases - isolation & purification Receptor Protein-Tyrosine Kinases - metabolism Substrate Specificity Transfection
G protein-coupled receptor kinases (GRKs), such as rhodopsin kinase and beta-adrenergic receptor kinase (beta ARK), are involved in mediating agonist-specific phosphorylation and desensitization of G protein-coupled receptors. GRK6 is the most recently identified member of the GRK family and displays higher homology with GRK5 (70.1% amino acid identity) and IT11 (68.5%) compared to beta ARK (37.4%) and rhodopsin kinase (47.1%). To further characterize GRK6, it has been overexpressed in Sf9 cells and purified to homogeneity by sequential chromatography on SP-Sepharose and heparin-Sepharose columns. GRK6 shares a number of in vitro characteristics with GRK5, including potent inhibition by heparin and dextran sulfate (IC50 values of approximately 15 and approximately 7 nM, respectively), hyperstimulation by polycations, and preference for phosphorylation of non-acidic peptides. Rhodopsin and the beta 2-adrenergic and m2 muscarinic cholinergic receptors serve as stimulus-dependent substrates for GRK6, but with stoichiometries significantly lower than achieved by GRK5 and beta ARK. Additionally, GRK6 does not undergo significant autophosphorylation even though it contains residues identical to those that are autophosphorylated in GRK5 and rhodopsin kinase. These data extend our knowledge of a growing family of receptor-specific kinases and suggest that GRK6 has a substrate specificity distinct from beta ARK, rhodopsin kinase, and GRK5.

Metrics

14 Record Views
81 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Web of Science research areas
Biochemistry & Molecular Biology
Logo image