Evidence map›Paper›PMID 19445518›Full record

ArticleBiochemistry2009

Structure and function of Vps15 in the endosomal G protein signaling pathway.

Erin J Heenan, Janeen L Vanhooke, Brenda R Temple, Laurie Betts, John E Sondek, Henrik G Dohlman

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

24 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
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  8. Mechanisms of Autophagy Initiation.Annual review of biochemistry · 2017
    Review
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  10. Dynamics and architecture of the NRBF2-containing phosphatidylinositol 3-kinase complex I of autophagy.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
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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

6 authors at 1 institution in 1 country.

Erin J HeenanDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599-7260, USA.
Janeen L Vanhooke
Brenda R Temple
Laurie Betts
John E Sondek
Henrik G Dohlman
University of North Carolina at Chapel Hill · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
G Protein Signaling at the endosomeR01GM080739 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DOHLMAN, HENRIK G. · 2007 to 2014
$2.6M
Modeling Feedback Regulation of Cell SignalingR01GM073180 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DOHLMAN, HENRIK G. · 2005 to 2012
$2.6M
GBeta5/RGS proteins and GPCR signalingR01GM081881 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SONDEK, JOHN E · 2007 to 2010
$1.1M
NCI NIH HHS P30 CA016086NIGMS NIH HHS GM080739NIGMS NIH HHS GM081881NIGMS NIH HHS R01 GM073180NIGMS NIH HHS R01 GM080739NIGMS NIH HHS R01 GM081881
6 · The paper itself

Abstract

G protein-coupled receptors mediate cellular responses to a wide variety of stimuli, including taste, light, and neurotransmitters. In the yeast Saccharomyces cerevisiae, activation of the pheromone pathway triggers events leading to mating. The view had long been held that the G protein-mediated signal occurs principally at the plasma membrane. Recently, it has been shown that the G protein alpha subunit Gpa1 can promote signaling at endosomes and requires two components of the sole phosphatidylinositol-3-kinase in yeast, Vps15 and Vps34. Vps15 contains multiple WD repeats and also binds to Gpa1 preferentially in the GDP-bound state; these observations led us to hypothesize that Vps15 may function as a G protein beta subunit at the endosome. Here we show an X-ray crystal structure of the Vps15 WD domain that reveals a seven-bladed propeller resembling that of typical Gbeta subunits. We show further that the WD domain is sufficient to bind Gpa1 as well as to Atg14, a potential Ggamma protein that exists in a complex with Vps15. The Vps15 kinase domain together with the intermediate domain (linking the kinase and WD domains) also contributes to Gpa1 binding and is necessary for Vps15 to sustain G protein signaling. These findings reveal that the Vps15 Gbeta-like domain serves as a scaffold to assemble Gpa1 and Atg14, whereas the kinase and intermediate domains are required for proper signaling at the endosome.

Indexed as

Signal TransductionBase SequenceCrystallography, X-RayDNA PrimersEndosomal Sorting Complexes Required for TransportEndosomesGTP-Binding ProteinsModels, MolecularPhosphorylationProtein Serine-Threonine KinasesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsStructure-Activity RelationshipVacuolar Sorting Protein VPS15DNA PrimersEndosomal Sorting Complexes Required for TransportGTP-Binding ProteinsProtein Serine-Threonine KinasesSaccharomyces cerevisiae ProteinsVacuolar Sorting Protein VPS15VPS15 protein, S cerevisiae

Identifiers

PMID19445518
PMCPMC2740480
OpenAlexW1974058577

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.