Evidence map›Paper›PMID 9742115›Full record

ArticleMolecular and cellular biology1998

Dominant-negative mutations in the G-protein-coupled alpha-factor receptor map to the extracellular ends of the transmembrane segments.

M Dosil, L Giot, C Davis, J B Konopka

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.2field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 54 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

M DosilDepartment of Molecular Genetics and Microbiology, State University of New York, Stony Brook, New York 11794-5222, USA.
L Giot
C Davis
J B Konopka
State University of New York · US

Funding

VIRAL ONCOLOGYT32CA009176 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI HEARING, PATRICK · 1985 to 2012
$5.2M
ACTIVATION OF G PROTEIN COUPLED RECEPTORSR01GM055107 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI KONOPKA, JAMES B. · 1997 to 2004
$1.2M
NCI NIH HHS 5T32CAO9176NCI NIH HHS T32 CA009176NIGMS NIH HHS GM55107NIGMS NIH HHS R01 GM055107
6 · The paper itself

Abstract

G-protein-coupled receptors (GPCRs) transduce the signals for a wide range of hormonal and sensory stimuli by activating a heterotrimeric guanine nucleotide-binding protein (G protein). The analysis of loss-of-function and constitutively active receptor mutants has helped to reveal the functional properties of GPCRs and their role in human diseases. Here we describe the identification of a new class of mutants, dominant-negative mutants, for the yeast G-protein-coupled alpha-factor receptor (Ste2p). Sixteen dominant-negative receptor mutants were isolated based on their ability to inhibit the response to mating pheromone in cells that also express wild-type receptors. Detailed analysis of two of the strongest mutant receptors showed that, unlike other GPCR interfering mutants, they were properly localized at the plasma membrane and did not alter the stability or localization of wild-type receptors. Furthermore, their dominant-negative effect was inversely proportional to the relative amount of wild-type receptors and was reversed by overexpressing the G-protein subunits, suggesting that these mutants compete with the wild-type receptors for the G protein. Interestingly, the dominant-negative mutations are all located at the extracellular ends of the transmembrane segments, defining a novel region of the receptor that is important for receptor signaling. Altogether, our results identify residues of the alpha-factor receptor specifically involved in ligand binding and receptor activation and define a new mechanism by which GPCRs can be inactivated that has important implications for the evaluation of receptor mutations in other G-protein-coupled receptors.

Indexed as

MutationTranscription FactorsAmino Acid SequenceBinding SitesExtracellular SpaceGene DosageGTP-Binding ProteinsMating FactorMolecular Sequence DataPeptidesPheromonesReceptors, Mating FactorReceptors, PeptideSaccharomyces cerevisiaeSubcellular FractionsGTP-Binding ProteinsMating FactorPeptidesPheromonesReceptors, Mating FactorReceptors, PeptideTranscription Factors

Identifiers

PMID9742115
PMCPMC109184
OpenAlexW1797452114

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.