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Proc Natl Acad Sci U S A

Title:		Mutations that alter the third cytoplasmic loop of the a-factor receptor lead to a constitutive and hypersensitive phenotype
Author(s):		Boone C; Davis NG; Sprague GF;
Address:		"Institute of Molecular Biology, University of Oregon, Eugene 97403"
Journal Title:		Proc Natl Acad Sci U S A
Year:		1993
Volume:		90
Issue:		21
Page Number:		9921 - 9925
DOI:		10.1073/pnas.90.21.9921
ISSN/ISBN:		0027-8424 (Print) 1091-6490 (Electronic) 0027-8424 (Linking)
Abstract:		"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"
Keywords:		"Alleles Amino Acid Sequence *Genes, Fungal Kinetics Mating Factor Molecular Sequence Data Mutagenesis Peptides/pharmacology Phenotype Pheromones/pharmacology *Point Mutation Protein Structure, Secondary Receptors, Mating Factor Receptors, Peptide/chemistr;"
Notes:		"MedlineBoone, C Davis, N G Sprague, G F Jr eng GM12672/GM/NIGMS NIH HHS/ GM38157/GM/NIGMS NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 1993/11/01 Proc Natl Acad Sci U S A. 1993 Nov 1; 90(21):9921-5. doi: 10.1073/pnas.90.21.9921"