Files and links (1)
Published, Version of Record (VoR)CC BY V4.0, Open
Journal article
Altered Activity of Palmitoylation-deficient and Isoprenylated Forms of the G Protein-coupled Receptor Kinase GRK6
The Journal of biological chemistry, v 272(43), pp 27422-27427
24 Oct 1997
PMID: 9341194
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
G protein-coupled receptor kinases (GRKs) utilize diverse mechanisms to associate with the plasma membrane and mediate phosphorylation of agonist-occupied receptors. For example, two members of this family, GRK4 and GRK6, contain C-terminal cysteine residues that are palmitoylated. To address whether the activity and membrane association of GRK6 is regulated by palmitoylation, we overexpressed and characterized wild-type GRK6 and two GRK6 mutants, one with the palmitoylation sites mutated to serines (GRK6-pal−) and one containing a C-terminal CAAX motif to promote geranylgeranylation (GRK6-GG). Compared with wild-type GRK6, GRK6-pal− had a ∼5-fold higher Km and ∼2-fold lower Vmax for phosphorylating rhodopsin, whereas GRK6-GG exhibited a ∼2-fold lowerKm and ∼14-fold higherVmax for rhodopsin. In contrast, wild-type GRK6 and GRK6-pal− displayed similar activity toward the nonreceptor substrate phosvitin, indicating that nonpalmitoylated GRK6 is catalytically active. Wild-type GRK6 and GRK6-GG, but not GRK6-pal−, also bound significantly to phosphatidylcholine vesicles (36 ± 3, 79 ± 4, and 4 ± 27, respectively) suggesting that GRK6 activity is dependent upon its ability to interact with the plasma membrane. When assayed in COS-1 cells GRK6-pal− promoted minimal agonist-dependent sequestration of the ॆ2-adrenergic receptor, while sequestration was significantly increased in cells expressing either wild-type GRK6 or GRK6-GG. These data demonstrate an important functional link between the ability of GRK6 to bind to the plasma membrane, a process that appears to be regulated by palmitoylation, and its activity toward receptor substrates.
Metrics
Details
- Title
- Altered Activity of Palmitoylation-deficient and Isoprenylated Forms of the G Protein-coupled Receptor Kinase GRK6
- Creators
- Robert P. LoudonJeffrey L. Benovic
- Publication Details
- The Journal of biological chemistry, v 272(43), pp 27422-27427
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:A1997YC65900090
- Scopus ID
- 2-s2.0-0030777365
- Other Identifier
- 991020950418704721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology