Evidence map›Paper›PMID 24928510›Full record

ArticleThe Journal of biological chemistry2014

Glucose activates TORC2-Gad8 protein via positive regulation of the cAMP/cAMP-dependent protein kinase A (PKA) pathway and negative regulation of the Pmk1 protein-mitogen-activated protein kinase pathway.

Adiel Cohen, Martin Kupiec, Ronit Weisman

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. 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
2.7field-weighted citation impact, top 10% 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, 49 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

3 authors at 1 institution in 1 country.

Adiel CohenFrom the Department of Natural and Life Sciences, Open University of Israel, University Road 1, 4353701 Ranana and.
Martin Kupiecthe Department of Molecular Microbiology and Biotechnology, Tel Aviv University, 69978 Tel Aviv, Israel.
Ronit WeismanFrom the Department of Natural and Life Sciences, Open University of Israel, University Road 1, 4353701 Ranana and ronitwe@openu.ac.il.
Tel Aviv University · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The target of rapamycin (TOR) kinase belongs to the highly conserved eukaryotic family of phosphatidylinositol 3-kinase-related kinases. TOR proteins are found at the core of two evolutionary conserved complexes, known as TORC1 and TORC2. In fission yeast, TORC2 is dispensable for proliferation under optimal growth conditions but is required for starvation and stress responses. TORC2 has been implicated in a wide variety of functions; however, the signals that regulate TORC2 activity have so far remained obscure. TORC2 has one known direct substrate, the AGC kinase Gad8, which is related to AKT in human cells. Gad8 is phosphorylated by TORC2 at Ser-546 (equivalent to AKT Ser-473), leading to its activation. Here, we show that glucose is necessary and sufficient to induce Gad8 Ser-546 phosphorylation in vivo and Gad8 kinase activity in vitro. The glucose signal that activates TORC2-Gad8 is mediated via the cAMP/PKA pathway, a major glucose-sensing pathway. By contrast, Pmk1, similar to human extracellular signal-regulated kinases and a major stress-induced mitogen activated protein kinase (MAPK) in fission yeast, inhibits TORC2-dependent Gad8 phosphorylation and activation. Inhibition of TORC2-Gad8 also occurs in response to ionic or osmotic stress, in a manner dependent on the cAMP/PKA and Pmk1-MAPK signaling pathways. Our findings highlight the significance of glucose availability in regulation of TORC2-Gad8 and indicate a novel link between the cAMP/PKA, Pmk1/MAPK, and TORC2-Gad8 signaling.

Indexed as

Cell WallCyclic AMPCyclic AMP-Dependent Protein KinasesGlucoseMechanistic Target of Rapamycin Complex 2Mitogen-Activated Protein KinasesMultiprotein ComplexesPhosphorylationProtein Serine-Threonine KinasesSchizosaccharomycesSchizosaccharomyces pombe ProteinsTOR Serine-Threonine KinasesCyclic AMPCyclic AMP-Dependent Protein KinasesGad8 protein, S pombeGlucoseMechanistic Target of Rapamycin Complex 2Mitogen-Activated Protein KinasesMultiprotein ComplexesPmk1 protein, S pombeProtein Serine-Threonine KinasesSchizosaccharomyces pombe ProteinsTOR Serine-Threonine KinasesCyclic AMP (cAMP)GAD8GlucoseMitogen-activated Protein Kinase (MAPK)Protein Kinase A (PKA)S. pombeStress ResponseTORC2

Identifiers

PMID24928510
PMCPMC4118131
OpenAlexW2021773076

What OpenQuestion holds

Textmetadata
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.