Regions of the alpha 1-adrenergic receptor involved in coupling to phosphatidylinositol hydrolysis and enhanced sensitivity of biological function.

Cotecchia, S

Exum, S

Caron, MG

Lefkowitz, RJ

United States

2013-09-24T17:25:08Z

1990-04

Regions of the hamster alpha 1-adrenergic receptor (alpha 1 AR) that are important in GTP-binding protein (G protein)-mediated activation of phospholipase C were determined by studying the biological functions of mutant receptors constructed by recombinant DNA techniques. A chimeric receptor consisting of the beta 2-adrenergic receptor (beta 2AR) into which the putative third cytoplasmic loop of the alpha 1AR had been placed activated phosphatidylinositol metabolism as effectively as the native alpha 1AR, as did a truncated alpha 1AR lacking the last 47 residues in its cytoplasmic tail. Substitutions of beta 2AR amino acid sequence in the intermediate portions of the third cytoplasmic loop of the alpha 1AR or at the N-terminal portion of the cytoplasmic tail caused marked decreases in receptor coupling to phospholipase C. Conservative substitutions of two residues in the C terminus of the third cytoplasmic loop (Ala293----Leu, Lys290----His) increased the potency of agonists for stimulating phosphatidylinositol metabolism by up to 2 orders of magnitude. These data indicate (i) that the regions of the alpha 1AR that determine coupling to phosphatidylinositol metabolism are similar to those previously shown to be involved in coupling of beta 2AR to adenylate cyclase stimulation and (ii) that point mutations of a G-protein-coupled receptor can cause remarkable increases in sensitivity of biological response.

http://www.ncbi.nlm.nih.gov/pubmed/2158097

0027-8424

https://hdl.handle.net/10161/7864

eng

Proceedings of the National Academy of Sciences

Proc Natl Acad Sci U S A

Amino Acid Sequence

Animals

Cell Line

Cricetinae

Hydrolysis

Inositol

Inositol Phosphates

Kinetics

Ligands

Molecular Sequence Data

Norepinephrine

Phosphatidylinositols

Plasmids

Protein Conformation

Receptors, Adrenergic, alpha

Regions of the alpha 1-adrenergic receptor involved in coupling to phosphatidylinositol hydrolysis and enhanced sensitivity of biological function.

Journal article

Lefkowitz, RJ|0000-0003-1472-7545

http://www.ncbi.nlm.nih.gov/pubmed/2158097

2896

2900

8

Basic Science Departments

Biochemistry

Cell Biology

Chemistry

Clinical Science Departments

Duke

Duke Cancer Institute

Duke Institute for Brain Sciences

Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Medicine, Cardiology

Neurobiology

Pathology

School of Medicine

Trinity College of Arts & Sciences

University Institutes and Centers

Published

87