Evidence map›Paper›PMID 21215374›Full record

ArticleCell2011

Tunable signal processing in synthetic MAP kinase cascades.

Ellen C O'Shaughnessy, Santhosh Palani, James J Collins, Casim A Sarkar

Abstract read
In one paragraph

Article in Cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed
–field-weighted citation impact
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

77 citing papers in PubMed.

  1. Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026
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  9. Network regulation meets substrate modification chemistry.Journal of the Royal Society, Interface · 2023
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  15. Investigating the Evolution and Development of Biological Systems from the Perspective of Thermo-Kinetics and Systems Theory.Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life · 2020
    Review
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  20. Article

17 more citing papers are in PubMed but not listed here.

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

4 authors.

Ellen C O'ShaughnessyHoward Hughes Medical Institute, Department of Biomedical Engineering, Center for Advanced Biotechnology, Boston University, MA 02215, USA.
Santhosh Palani
James J Collins
Casim A Sarkar

Funding

A Network Biology Approach to Antibiotic Action and Bacterial Defense MechanismsDP1OD003644 · OD · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI COLLINS, JAMES J · 2007 to 2011
$4.1M
Howard Hughes Medical InstituteNIH HHS DP1 OD00364NIH HHS DP1 OD003644
6 · The paper itself

Abstract

The flexibility of MAPK cascade responses enables regulation of a vast array of cell fate decisions, but elucidating the mechanisms underlying this plasticity is difficult in endogenous signaling networks. We constructed insulated mammalian MAPK cascades in yeast to explore how intrinsic and extrinsic perturbations affect the flexibility of these synthetic signaling modules. Contrary to biphasic dependence on scaffold concentration, we observe monotonic decreases in signal strength as scaffold concentration increases. We find that augmenting the concentration of sequential kinases can enhance ultrasensitivity and lower the activation threshold. Further, integrating negative regulation and concentration variation can decouple ultrasensitivity and threshold from the strength of the response. Computational analyses show that cascading can generate ultrasensitivity and that natural cascades with different kinase concentrations are innately biased toward their distinct activation profiles. This work demonstrates that tunable signal processing is inherent to minimal MAPK modules and elucidates principles for rational design of synthetic signaling systems.

Indexed as

MAP Kinase Signaling SystemModels, BiologicalSignal TransductionAnimalsHumansSaccharomyces cerevisiaeSynthetic Biology

Identifiers

PMID21215374
PMCPMC3035479

What OpenQuestion holds

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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.