Evidence map›Paper›PMID 31856761›Full record

ArticleBMC cancer2019

Direct physical interaction of active Ras with mSIN1 regulates mTORC2 signaling.

Mehraj-U-Din Lone, Javed Miyan, Mohammad Asif, Showkat A Malik, Parul Dubey, Varsha Singh, Kavita Singh, Kalyan Mitra, Deepali Pandey, Wahajul Haq and 6 more

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.1field-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

17 citing papers in PubMed, 23 citations in OpenAlex.

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  14. Ras, PI3K and mTORC2 - three's a crowd?Journal of cell science · 2020
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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

16 authors at 4 institutions in 3 countries.

Mehraj-U-Din LoneDivision of Toxicology and Experimental Medicine, Central Drug Research Institute (CSIR), Lucknow, Uttar Pradesh, 226031, India.
Javed MiyanDivision of Toxicology and Experimental Medicine, Central Drug Research Institute (CSIR), Lucknow, Uttar Pradesh, 226031, India.
Mohammad AsifDivision of Toxicology and Experimental Medicine, Central Drug Research Institute (CSIR), Lucknow, Uttar Pradesh, 226031, India.
Showkat A MalikDivision of Toxicology and Experimental Medicine, Central Drug Research Institute (CSIR), Lucknow, Uttar Pradesh, 226031, India.
Parul DubeyDepartment of Surgical Oncology, King George Medical University, Lucknow, Uttar Pradesh, 226003, India.
Varsha SinghDivision of Toxicology and Experimental Medicine, Central Drug Research Institute (CSIR), Lucknow, Uttar Pradesh, 226031, India.
Kavita SinghElectron Microscopy Unit, Sophisticated Analytical Instrumentation Facility, Central Drug Research Institute (CSIR), Lucknow, Uttar Pradesh, 226031, India.
Kalyan MitraAcademy of Scientific and Innovative Research (AcSIR), New Delhi, 110025, India.
Deepali PandeyMedicinal and Process Chemistry Division, Central Drug Research Institute (CSIR), Lucknow, Uttar Pradesh, 226031, India.
Wahajul HaqMedicinal and Process Chemistry Division, Central Drug Research Institute (CSIR), Lucknow, Uttar Pradesh, 226031, India.
Himanshi AmitaDivision of Toxicology and Experimental Medicine, Central Drug Research Institute (CSIR), Lucknow, Uttar Pradesh, 226031, India.
Prince Kumar SinghDivision of Toxicology and Experimental Medicine, Central Drug Research Institute (CSIR), Lucknow, Uttar Pradesh, 226031, India.
Wieland KiessCenter for Pediatric Research Leipzig, University Hospital for Children and Adolescents, Faculty of Medicine, University of Leipzig, Leipzig, Germany.
Franziska KaessnerCenter for Pediatric Research Leipzig, University Hospital for Children and Adolescents, Faculty of Medicine, University of Leipzig, Leipzig, Germany.
Antje GartenCenter for Pediatric Research Leipzig, University Hospital for Children and Adolescents, Faculty of Medicine, University of Leipzig, Leipzig, Germany.
Smrati BhadauriaDivision of Toxicology and Experimental Medicine, Central Drug Research Institute (CSIR), Lucknow, Uttar Pradesh, 226031, India. smriti_bhadauria@cdri.res.in.ORCID http://orcid.org/0000-0002-9014-7027
Central Drug Research Institute · INLeipzig University · DEKing George's Medical University · INUniversity of Birmingham · GB

Funding

Deutsche Forschungsgemeinschaft GA2228/2-1DST-SERB EMR/2016/006323Indian National Science Academy 2016
6 · The paper itself

Abstract

backgroundThe mechanistic (or mammalian) target of rapamycin (mTOR), a Ser/Thr kinase, associates with different subunits forming two functionally distinct complexes, mTORC1 and mTORC2, regulating a diverse set of cellular functions in response to growth factors, cellular energy levels, and nutrients. The mechanisms regulating mTORC1 activity are well characterized; regulation of mTORC2 activity, however, remains obscure. While studies conducted in Dictyostelium suggest a possible role of Ras protein as a potential upstream regulator of mTORC2, definitive studies delineating the underlying molecular mechanisms, particularly in mammalian cells, are still lacking.

methodsProtein levels were measured by Western blotting and kinase activity of mTORC2 was analyzed by in vitro kinase assay. In situ Proximity ligation assay (PLA) and co-immunoprecipitation assay was performed to detect protein-protein interaction. Protein localization was investigated by immunofluorescence and subcellular fractionation while cellular function of mTORC2 was assessed by assaying extent of cell migration and invasion.

resultsHere, we present experimental evidence in support of the role of Ras activation as an upstream regulatory switch governing mTORC2 signaling in mammalian cancer cells. We report that active Ras through its interaction with mSIN1 accounts for mTORC2 activation, while disruption of this interaction by genetic means or via peptide-based competitive hindrance, impedes mTORC2 signaling.

conclusionsOur study defines the regulatory role played by Ras during mTORC2 signaling in mammalian cells and highlights the importance of Ras-mSIN1 interaction in the assembly of functionally intact mTORC2.

Indexed as

Cell Line, TumorCell MovementCell ProliferationHumansLipomaMCF-7 CellsMechanistic Target of Rapamycin Complex 2Monomeric GTP-Binding ProteinsMutationNeoplasmsPC-3 Cellsras ProteinsSignal TransductionSuperoxidesUp-RegulationMechanistic Target of Rapamycin Complex 2Monomeric GTP-Binding ProteinsmSin1 protein, humanras ProteinsSuperoxidesCancerMammalian target of rapamycin (mTOR)RasSignalingSuperoxide anion

Identifiers

PMID31856761
PMCPMC6921532
OpenAlexW2995849886

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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.