Mutations that alter the third cytoplasmic loop of the a-factor receptor lead to a constitutive and hypersensitive phenotype

The STE3 gene of Saccharomyces cerevisiae encodes a G protein-coupled receptor that is specific for the mating pheromone a-factor. The ste3L194Q mutation, which leads to the substitution of glutamine for leucine-194 within the third cytoplasmic loop of the receptor, resulted in a 20-fold increase in...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1993-11, Vol.90 (21), p.9921-9925
Main Authors: Boone, C, Davis, N.G, Sprague, G.F. Jr
Format: Article
Language:English
Subjects:
Alleles
Amino Acid Sequence
Biological and medical sciences
Cell cycle
Cell receptors
Cell structures and functions
EXPRESION GENICA
EXPRESSION DES GENES
FENOTIPOS
FEROMONAS
Fundamental and applied biological sciences. Psychology
Genes, Fungal
Genetic loci
Genetic mutation
Genetics
Hypersensitivity
Kinetics
LEVADURA
LEVURE
Mating Factor
Miscellaneous
Molecular and cellular biology
Molecular Sequence Data
MUTACION
Mutagenesis
MUTATION
Peptides - pharmacology
PHENOTYPE
Phenotypes
PHEROMONE
Pheromones
Pheromones - pharmacology
PLASMIDE
PLASMIDIOS
Plasmids
Point Mutation
Protein Structure, Secondary
Proteins
REACCIONES ALERGICAS
REACTION ALLERGIQUE
Receptors
Receptors, Mating Factor
Receptors, Peptide - chemistry
Receptors, Peptide - genetics
Receptors, Peptide - metabolism
Recombinant Fusion Proteins - biosynthesis
Recombinant Fusion Proteins - chemistry
Recombinant Fusion Proteins - metabolism
SACCHAROMYCES CEREVISIAE
Saccharomyces cerevisiae - drug effects
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Sequence Deletion
Transcription Factors
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Description
Summary:The STE3 gene of Saccharomyces cerevisiae encodes a G protein-coupled receptor that is specific for the mating pheromone a-factor. The ste3L194Q mutation, which leads to the substitution of glutamine for leucine-194 within the third cytoplasmic loop of the receptor, resulted in a 20-fold increase in pheromone sensitivity and also caused partial constitutive activation of the response pathway. Moreover, other amino acid substitutions at the 194 position and several deletion mutations that collectively remove most of the third cytoplasmic loop resulted in hyperactive receptors. Therefore, we suggest that one role of the third cytoplasmic loop is to function as a negative regulatory domain involved in the maintenance of a nonsignaling state of the receptor. The constitutive activity and the pheromone hypersensitivity of ste3L194Q cells were recessive, suggesting that the wild-type receptor can antagonize the signal associated with the activated receptor. The ste3 delta 306 mutation, which results in truncation of most of the C-terminal domain of the receptor, led to a 20-fold increase in pheromone sensitivity, indicating that this domain also mediates negative regulation of the receptor. The ste3L194Q and ste3 delta 306 mutations appear to affect receptor activity independently, because the double mutant was associated with a 400-fold increase in pheromone sensitivity
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.90.21.9921