Evidence map›Paper›PMID 26169833›Full record

ArticleMolecular and cellular biology2015

p110α Hot Spot Mutations E545K and H1047R Exert Metabolic Reprogramming Independently of p110α Kinase Activity.

Aditi Chaudhari, Daniel Krumlinde, Annika Lundqvist, Levent M Akyürek, Sashidhar Bandaru, Kristina Skålén, Marcus Ståhlman, Jan Borén, Yvonne Wettergren, Katarina Ejeskär and 1 more

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In one paragraph

Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 35% 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

3 citing papers in PubMed, 4 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

11 authors at 1 institution in 1 country.

Aditi ChaudhariWallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
Daniel KrumlindeWallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
Annika LundqvistWallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
Levent M AkyürekDepartment of Medical Chemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden.
Sashidhar BandaruDepartment of Medical Chemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden.
Kristina SkålénWallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
Marcus StåhlmanWallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
Jan BorénWallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
Yvonne WettergrenDepartment of Surgery, University of Gothenburg, Gothenburg, Sweden.
Katarina EjeskärDepartment of Medical and Clinical Genetics, University of Gothenburg, Gothenburg, Sweden Systems Biology Research Center, University of Skövde, Skövde, Sweden.
Victoria Rotter SopasakisWallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden victoria.rotter@wlab.gu.se.
University of Gothenburg · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) catalytic subunit p110α is the most frequently mutated kinase in human cancer, and the hot spot mutations E542K, E545K, and H1047R are the most common mutations in p110α. Very little is known about the metabolic consequences of the hot spot mutations of p110α in vivo. In this study, we used adenoviral gene transfer in mice to investigate the effects of the E545K and H1047R mutations on hepatic and whole-body glucose metabolism. We show that hepatic expression of these hot spot mutations results in rapid hepatic steatosis, paradoxically accompanied by increased glucose tolerance, and marked glycogen accumulation. In contrast, wild-type p110α expression does not lead to hepatic accumulation of lipids or glycogen despite similar degrees of upregulated glycolysis and expression of lipogenic genes. The reprogrammed metabolism of the E545K and H1047R p110α mutants was surprisingly not dependent on altered p110α lipid kinase activity.

Indexed as

Energy MetabolismMutation, MissenseAnimalsClass I Phosphatidylinositol 3-KinasesEnzyme ActivationFatty AcidsFatty LiverGlucose IntoleranceGlycogenGlycolysisLipid MetabolismLiverMaleMice, KnockoutOxidation-ReductionPhosphorylation1-phosphatidylinositol 3-kinase p110 subunit, mouseClass I Phosphatidylinositol 3-KinasesFatty AcidsGlycogenProto-Oncogene Proteins c-akt

Identifiers

PMID26169833
PMCPMC4561724
OpenAlexW1925227769

What OpenQuestion holds

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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.