Evidence map›Paper›PMID 12832470›Full record

ArticleMolecular and cellular biology2003

Combination of two activating mutations in one HOG1 gene forms hyperactive enzymes that induce growth arrest.

Gilad Yaakov, Michal Bell, Stefan Hohmann, David Engelberg

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

22 citing papers in PubMed, 57 citations in OpenAlex.

  1. Article
  2. Review
  3. Active p38α causes macrovesicular fatty liver in mice.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  4. Article
  5. Article
  6. Non-canonical Activities of Hog1 Control Sensitivity ofFrontiers in cellular and infection microbiology · 2018
    Article
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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

4 authors at 2 institutions in 4 countries.

Gilad YaakovDepartment of Biological Chemistry, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Michal Bell
Stefan Hohmann
David Engelberg
Hebrew University of Jerusalem · ILUniversity of Gothenburg · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mitogen-activated protein kinases (MAPKs) play key roles in differentiation, growth, proliferation, and apoptosis. Although MAPKs have been extensively studied, the precise function, specific substrates, and target genes of each MAPK are not known. These issues could be addressed by sole activation of a given MAPK, e.g., through the use of constitutively active MAPK enzymes. We have recently reported the isolation of eight hyperactive mutants of the Saccharomyces cerevisiae MAPK Hog1, each of which bears a distinct single point mutation. These mutants acquired high intrinsic catalytic activity but did not impose the full biological potential of the Hog1 pathway. Here we describe our attempt to obtain a MAPK that is more active than the previous mutants both catalytically and biologically. We combined two different activating point mutations in the same gene and found that two of the resulting double mutants acquired unusual properties. These alleles, HOG1(D170A,F318L) and HOG1(D170A,F318S), induced a severe growth inhibition and had to be studied through an inducible expression system. This growth inhibition correlated with very high spontaneous (in the absence of any stimulation) catalytic activity and strong induction of Hog1 target genes. Furthermore, analysis of the phosphorylation status of these active alleles shows that their acquired intrinsic activity is independent of either phospho-Thr174 or phospho-Tyr176. Through fluorescence-activated cell sorting analysis, we show that the effect on cell growth inhibition is not a result of cell death. This study provides the first example of a MAPK that is intrinsically activated by mutations and induces a strong biological effect.

Indexed as

MutationCatalysisCell DivisionEnzyme ActivationGene Expression Regulation, FungalMitogen-Activated Protein KinasesOsmotic PressurePhosphorylationPromoter Regions, GeneticSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsThreonineTyrosineHOG1 protein, S cerevisiaeMitogen-Activated Protein KinasesSaccharomyces cerevisiae ProteinsThreonineTyrosine

Identifiers

PMID12832470
PMCPMC162220
OpenAlexW2101190129

What OpenQuestion holds

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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.