Evidence map›Paper›PMID 22878499›Full record

ArticleScience (New York, N.Y.)2012

Conformational control of the Ste5 scaffold protein insulates against MAP kinase misactivation.

Jesse G Zalatan, Scott M Coyle, Saravanan Rajan, Sachdev S Sidhu, Wendell A Lim

Open access · bronzeAbstract read
In one paragraph

Article in Science (New York, N.Y.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
6.4field-weighted citation impact, top 2% 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

48 citing papers in PubMed, 99 citations in OpenAlex.

  1. Article
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  13. Preferences in a trait decision determined by transcription factor variants.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  14. Article
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  18. Article
  19. Structural basis of autoregulatory scaffolding by apoptosis signal-regulating kinase 1.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Jesse G ZalatanDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, 600 16th Street, San Francisco, CA 94158, USA.
Scott M Coyle
Saravanan Rajan
Sachdev S Sidhu
Wendell A Lim
University of California, San Francisco · US

Funding

YEAST THREONINE &SERINE KINASESP41RR001614 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ORTIZ DE MONTELLANO, PAUL R · 1985 to 2011
$24.1M
Rewiring Therapeutic Cells: User-Controlled T Cells and Stem CellsP50GM081879 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A · 2010 to 2017
$19.0M
Cellular Control:Synthetic Signaling/Motility (RMI)PN2EY016546 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A · 2005 to 2014
$16.0M
PROTEIN RECOGNITION IN SIGNAL TRANSDUCTIONR01GM055040 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A · 1997 to 2015
$3.5M
PROTEIN INTERACTIONS REGULATING CELL MOTILITYR01GM062583 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A · 2001 to 2009
$2.2M
CIHR MOPS-93725Howard Hughes Medical InstituteNCRR NIH HHS P41 RR001614NEI NIH HHS PN2 EY016546NIGMS NIH HHS P50 GM081879NIGMS NIH HHS R01 GM055040NIGMS NIH HHS R01 GM062583NIGMS NIH HHS R01 GM55040NIGMS NIH HHS R01 GM62583
6 · The paper itself

Abstract

Cells reuse signaling proteins in multiple pathways, raising the potential for improper cross talk. Scaffold proteins are thought to insulate against such miscommunication by sequestering proteins into distinct physical complexes. We show that the scaffold protein Ste5, which organizes the yeast mating mitogen-activated protein kinase (MAPK) pathway, does not use sequestration to prevent misactivation of the mating response. Instead, Ste5 appears to use a conformation mechanism: Under basal conditions, an intramolecular interaction of the pleckstrin homology (PH) domain with the von Willebrand type A (VWA) domain blocks the ability to coactivate the mating-specific MAPK Fus3. Pheromone-induced membrane binding of Ste5 triggers release of this autoinhibition. Thus, in addition to serving as a conduit guiding kinase communication, Ste5 directly receives input information to decide if and when signal can be transmitted to mating output.

Indexed as

Adaptor Proteins, Signal TransducingEnzyme ActivationMAP Kinase Kinase KinasesMAP Kinase Signaling SystemMitogen-Activated Protein Kinase KinasesMitogen-Activated Protein KinasesModels, BiologicalPhosphorylationProtein ConformationProtein Interaction Domains and MotifsProtein KinasesProtein PrecursorsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsAdaptor Proteins, Signal TransducingFUS3 protein, S cerevisiaeMAP Kinase Kinase KinasesMF(ALPHA)1 protein, S cerevisiaeMitogen-Activated Protein Kinase KinasesMitogen-Activated Protein KinasesProtein KinasesProtein PrecursorsSaccharomyces cerevisiae ProteinsSte11 protein, S cerevisiaeSTE5 protein, S cerevisiaeSTE7 protein, S cerevisiae

Identifiers

PMID22878499
PMCPMC3631425
OpenAlexW2011396562

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.