Evidence map›Paper›PMID 21666717›Full record

ArticleOncogene2011

Kinome siRNA-phosphoproteomic screen identifies networks regulating AKT signaling.

Y Lu, M Muller, D Smith, B Dutta, K Komurov, S Iadevaia, D Ruths, J T Tseng, S Yu, Q Yu and 8 more

Abstract read
In one paragraph

Article in Oncogene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
5.3field-weighted citation impact, top 3% 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

42 citing papers in PubMed, 65 citations in OpenAlex.

  1. Clinical activity and safety of combination therapy with temsirolimus and bevacizumab for advanced melanoma: a phase II trial (CTEP 7190/Mel47).Clinical cancer research : an official journal of the American Association for Cancer Research · 2013
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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

18 authors at 4 institutions in 2 countries.

Y LuDepartment of Systems Biology, UT MD Anderson Cancer Center, Houston, TX 77054, USA.
M Muller
D Smith
B Dutta
K Komurov
S Iadevaia
D Ruths
J T Tseng
S Yu
Q Yu
L Nakhleh
G Balazsi
J Donnelly
M Schurdak
S Morgan-Lappe
S Fesik
P T Ram
G B Mills
The University of Texas MD Anderson Cancer Center · USAbbott Fund · USRice University · USCenter for Systems Biology · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
UNIVERSITY OF TEXAS MD ANDERSON SPORE IN OVARIAN CANCERP50CA083639 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BAST, ROBERT C · 1999 to 2015
$33.0M
Targeting the PI3K Signaling Pathway in Endometrial CarcinomaP50CA098258 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BODURKA, DIANE · 2003 to 2020
$32.0M
Systems-Based Predictions of Responses to Cancer TherapyU54CA112970 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI MILLS, GORDON B. · 2004 to 2014
$27.1M
Tyrosine Kinase-Dependant and - Independent Pathways of EGFR in Breast Cancer ProP01CA099031 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HUNG, MIEN-CHIE · 2003 to 2014
$11.6M
Training in Pharmacoinformatics(RMI)T90DK070109 · NIDDK · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI STANCEL, GEORGE M. · 2004 to 2008
$1.6M
Determinants of signaling network regulation in combinatorial targeted therapiesR01CA125109 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI RAM, PRAHLAD T · 2008 to 2010
$1.1M
NCI NIH HHS P01 CA099031NCI NIH HHS P01CA099031NCI NIH HHS P30 CA016672NCI NIH HHS P30CA16672NCI NIH HHS P50 CA083639NCI NIH HHS P50CA083639NCI NIH HHS R01 CA125109NCI NIH HHS R01CA125109NCI NIH HHS U54 CA112970NIDDK NIH HHS T90 DK070109NIDDK NIH HHS T90DK070109PHS HHS DPA86424-444938
6 · The paper itself

Abstract

To identify regulators of intracellular signaling, we targeted 541 kinases and kinase-related molecules with small interfering RNAs (siRNAs), and determined their effects on signaling with a functional proteomics reverse-phase protein array (RPPA) platform assessing 42 phospho and total proteins. The kinome-wide screen demonstrated a strong inverse correlation between phosphorylation of AKT and mitogen-activated protein kinase (MAPK) with 115 genes that, when targeted by siRNAs, demonstrated opposite effects on MAPK and AKT phosphorylation. Network-based analysis identified the MAPK subnetwork of genes along with p70S6K and FRAP1 as the most prominent targets that increased phosphorylation of AKT, a key regulator of cell survival. The regulatory loops induced by the MAPK pathway are dependent on tuberous sclerosis complex 2 but demonstrate a lesser dependence on p70S6K than the previously identified FRAP1 feedback loop. The siRNA screen also revealed novel bi-directionality in the AKT and GSK3 (Glycogen synthase kinase 3) interaction, whereby genetic ablation of GSK3 significantly blocks AKT phosphorylation, an unexpected observation as GSK3 has only been predicted to be downstream of AKT. This method uncovered novel modulators of AKT phosphorylation and facilitated the mapping of regulatory loops.

Indexed as

Cell Line, TumorCell SurvivalHumansMetabolic Networks and PathwaysPhosphoproteinsPhosphorylationProteomicsProto-Oncogene Proteins c-aktRNA, Small InterferingSignal TransductionTuberous Sclerosis Complex 2 ProteinTumor Suppressor ProteinsPhosphoproteinsProto-Oncogene Proteins c-aktRNA, Small InterferingTuberous Sclerosis Complex 2 ProteinTumor Suppressor Proteins

Identifiers

PMID21666717
PMCPMC3175328
OpenAlexW1990678347

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.