PALMITOYLATION OF THE HUMAN BETA-2-ADRENERGIC RECEPTOR - MUTATION OF CYS-341 IN THE CARBOXYL TAIL LEADS TO AN UNCOUPLED NONPALYMITOYLATED FORM OF THE RECEPTOR
- 5 May 1989
- journal article
- research article
- Vol. 264 (13) , 7564-7569
Abstract
We report that a cysteine residue in the human .beta.2-adrenergic receptor (.beta.2AR) is covalently modified by thioesterification with palmitic acid. By site-directed mutagenesis of the receptor, we have identified Cys341 in the carboxy tail of the protein as the most likely site of palmitolylation. Mutation of Cys341 to glycine results in a nonpalmitoylated form of the receptor that exhibits a drastically reduced ability to mediate isoproterenol stimulation of adenylyl cyclase. The functional impairment of this mutated .beta.2AR is also reflected in a markedly reduced ability to form a guanyl nucleotide-sensitive high affinity state for agonists, characteristic of wild-type receptor. These results indicate that post-translational modification by palmitate of .beta.2AR may play a crucial role in the normal coupling of the receptor to the adenylyl cyclase signal transduction system.This publication has 18 references indexed in Scilit:
- Regulation of adrenergic receptor function by phosphorylation. II. Effects of agonist occupancy on phosphorylation of alpha 1- and beta 2-adrenergic receptors by protein kinase C and the cyclic AMP-dependent protein kinase.Journal of Biological Chemistry, 1987
- Identification of the intermolecular disulfide bonds of the human transferrin receptor and its lipid-attachment site.The EMBO Journal, 1987
- The HLA-D-associated invariant chain binds palmitic acid at the cysteine adjacent to the membrane segment.Journal of Biological Chemistry, 1986
- Acylation of bovine rhodopsin by [3H]palmitic acid.Journal of Biological Chemistry, 1984
- The presence of cysteine in the cytoplasmic domain of the vesicular stomatitis virus glycoprotein is required for palmitate addition.Proceedings of the National Academy of Sciences, 1984
- Regression analysis of nonlinear Arrhenius plots: An empirical model and a computer programComputers in Biology and Medicine, 1984
- Purification of the beta-adrenergic receptor. Identification of the hormone binding subunit.Journal of Biological Chemistry, 1981
- Covalent binding of fatty acid to the transferrin receptor in cultured human cells.Journal of Biological Chemistry, 1981
- LIGAND: A versatile computerized approach for characterization of ligand-binding systemsAnalytical Biochemistry, 1980
- A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye BindingAnalytical Biochemistry, 1976