Evidence map›Paper›PMID 21423148›Full record

ArticleThe EMBO journal2011

MO25 is a master regulator of SPAK/OSR1 and MST3/MST4/YSK1 protein kinases.

Beatrice M Filippi, Paola de los Heros, Youcef Mehellou, Iva Navratilova, Robert Gourlay, Maria Deak, Lorna Plater, Rachel Toth, Elton Zeqiraj, Dario R Alessi

Open access · greenAbstract read
In one paragraph

Article in The EMBO journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed
5.6field-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

84 citing papers in PubMed, 137 citations in OpenAlex.

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  14. LKB1 biology: assessing the therapeutic relevancy of LKB1 inhibitors.Cell communication and signaling : CCS · 2024
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24 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

10 authors at 2 institutions in 1 country.

Beatrice M FilippiMRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee, UK. bfilippi@uhnresearch.ca
Paola de los Heros
Youcef Mehellou
Iva Navratilova
Robert Gourlay
Maria Deak
Lorna Plater
Rachel Toth
Elton Zeqiraj
Dario R Alessi
University of Dundee · GBMRC Protein Phosphorylation and Ubiquitylation Unit · GB

Funding

Medical Research Council MC_U127070193
6 · The paper itself

Abstract

Mouse protein-25 (MO25) isoforms bind to the STRAD pseudokinase and stabilise it in a conformation that can activate the LKB1 tumour suppressor kinase. We demonstrate that by binding to several STE20 family kinases, MO25 has roles beyond controlling LKB1. These new MO25 targets are SPAK/OSR1 kinases, regulators of ion homeostasis and blood pressure, and MST3/MST4/YSK1, involved in controlling development and morphogenesis. Our analyses suggest that MO25α and MO25β associate with these STE20 kinases in a similar manner to STRAD. MO25 isoforms induce approximately 100-fold activation of SPAK/OSR1 dramatically enhancing their ability to phosphorylate the ion cotransporters NKCC1, NKCC2 and NCC, leading to the identification of several new phosphorylation sites. siRNA-mediated reduction of expression of MO25 isoforms in mammalian cells inhibited phosphorylation of endogenous NKCC1 at residues phosphorylated by SPAK/OSR1, which is rescued by re-expression of MO25α. MO25α/β binding to MST3/MST4/YSK1 also stimulated kinase activity three- to four-fold. MO25 has evolved as a key regulator of a group of STE20 kinases and may represent an ancestral mechanism of regulating conformation of pseudokinases and activating catalytically competent protein kinases.

Indexed as

AnimalsCalcium-Binding ProteinsEnzyme ActivationEscherichia coliHEK293 CellsHippo KinasesHomeostasisHumansImmunoblottingInsectaIntracellular Signaling Peptides and ProteinsMorphogenesisPhosphorylationProtein IsoformsProtein Serine-Threonine KinasesRNA, Small InterferingCAB39 protein, humanCalcium-Binding ProteinsHippo KinasesIntracellular Signaling Peptides and ProteinsOXSR1 protein, humanProtein IsoformsProtein Serine-Threonine KinasesRNA, Small InterferingSTK25 protein, humanSTK26 protein, humanSTK39 protein, human

Identifiers

PMID21423148
PMCPMC3101989
OpenAlexW2146497623

What OpenQuestion holds

Textmetadata
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.