Evidence map›Paper›PMID 29547722›Full record

ArticleMolecular cell2018

CDK and MAPK Synergistically Regulate Signaling Dynamics via a Shared Multi-site Phosphorylation Region on the Scaffold Protein Ste5.

María Victoria Repetto, Matthew J Winters, Alan Bush, Wolfgang Reiter, David Maria Hollenstein, Gustav Ammerer, Peter M Pryciak, Alejandro Colman-Lerner

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.5field-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

29 citing papers in PubMed, 58 citations in OpenAlex.

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  10. PROBABILISTIC LEARNING OF TREATMENT TREES IN CANCER.The annals of applied statistics · 2023
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  14. Hyperosmolality in CHO cell culture: effects on the proteome.Applied microbiology and biotechnology · 2022
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  17. BRAF Controls the Effects of Metformin on Neuroblast Cell Divisions inInternational journal of molecular sciences · 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

8 authors at 5 institutions in 3 countries.

María Victoria RepettoDepartamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), C1428EGA Buenos Aires, Argentina; CONICET-UBA, Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Buenos Aires C1428EHA, Argentina.
Matthew J WintersDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Alan BushDepartamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), C1428EGA Buenos Aires, Argentina; CONICET-UBA, Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Buenos Aires C1428EHA, Argentina.
Wolfgang ReiterDepartment for Biochemistry, Max F. Perutz Laboratories, University of Vienna, Vienna 1030, Austria.
David Maria HollensteinDepartment for Biochemistry, Max F. Perutz Laboratories, University of Vienna, Vienna 1030, Austria.
Gustav AmmererDepartment for Biochemistry, Max F. Perutz Laboratories, University of Vienna, Vienna 1030, Austria.
Peter M PryciakDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: peter.pryciak@umassmed.edu.
Alejandro Colman-LernerDepartamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), C1428EGA Buenos Aires, Argentina; CONICET-UBA, Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Buenos Aires C1428EHA, Argentina. Electronic address: colman-lerner@fbmc.fcen.uba.ar.
Max Perutz Labs · ATUniversity of Massachusetts Chan Medical School · USInstitute of Astronomy and Space Physics · ARInstituto de Neurología de Buenos Aires · ARUniversity of Buenos Aires · AR

Funding

YEAST PHEROMONE SIGNAL TRANSDUCTIONR01GM057769 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI PRYCIAK, PETER M · 1997 to 2023
$7.6M
Dynamics of gradient sensing in single cellsR01GM097479 · NIGMS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BRENT, ROGER · 2011 to 2014
$2.1M
NIGMS NIH HHS R01 GM057769NIGMS NIH HHS R01 GM097479
6 · The paper itself

Abstract

We report an unanticipated system of joint regulation by cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK), involving collaborative multi-site phosphorylation of a single substrate. In budding yeast, the protein Ste5 controls signaling through a G1 arrest pathway. Upon cell-cycle entry, CDK inhibits Ste5 via multiple phosphorylation sites, disrupting its membrane association. Using quantitative time-lapse microscopy, we examined Ste5 membrane recruitment dynamics at different cell-cycle stages. Surprisingly, in S phase, where Ste5 recruitment should be blocked, we observed an initial recruitment followed by a steep drop-off. This delayed inhibition revealed a requirement for both CDK activity and negative feedback from the pathway MAPK Fus3. Mutagenesis, mass spectrometry, and electrophoretic analyses suggest that the CDK and MAPK modify shared sites, which are most extensively phosphorylated when both kinases are active and able to bind their docking sites on Ste5. Such collaborative phosphorylation can broaden regulatory inputs and diversify output dynamics of signaling pathways.

Indexed as

Signal TransductionAdaptor Proteins, Signal TransducingBinding SitesCell Cycle CheckpointsCell MembraneCyclin-Dependent KinasesCyclinsKineticsMitogen-Activated Protein KinasesPhosphorylationProtein BindingSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSubstrate SpecificityAdaptor Proteins, Signal TransducingCLN1 protein, S cerevisiaeCLN2 protein, S cerevisiaeCyclin-Dependent KinasesCyclinsFUS3 protein, S cerevisiaeMitogen-Activated Protein KinasesSaccharomyces cerevisiae ProteinsSTE5 protein, S cerevisiaeCdc28Cks1Cln2cyclinG proteinmatingpheromonesignal transductionstartSte4

Identifiers

PMID29547722
PMCPMC5858200
OpenAlexW2793849443

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.