Evidence map›Paper›PMID 27422819›Full record

ArticleThe Journal of biological chemistry2016

Follicle-Stimulating Hormone (FSH)-dependent Regulation of Extracellular Regulated Kinase (ERK) Phosphorylation by the Mitogen-activated Protein (MAP) Kinase Phosphatase MKP3.

Elyse M Donaubauer, Nathan C Law, Mary E Hunzicker-Dunn

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2016. 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
7.0field-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

22 citing papers in PubMed, 45 citations in OpenAlex.

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  18. Effects of Fullerenol Nanoparticles on Rat Oocyte Meiosis Resumption.International journal of molecular sciences · 2018
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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

3 authors at 1 institution in 1 country.

Elyse M DonaubauerFrom the School of Molecular Biosciences, Washington State University, Pullman, Washington 99164.
Nathan C LawFrom the School of Molecular Biosciences, Washington State University, Pullman, Washington 99164.
Mary E Hunzicker-DunnFrom the School of Molecular Biosciences, Washington State University, Pullman, Washington 99164 mehd@wsu.edu.ORCID 0000-0003-4640-1814
Washington State University · US

Funding

Functional Significance of the HIF1 Transcriptome in Granulosa CellsR01HD065859 · NICHD · WASHINGTON STATE UNIVERSITY · PI HUNZICKER-DUNN, MARY E, NILSON, JOHN H. · 2010 to 2014
$1.5M
Molecular Bioscience Graduate Training ProgramT32GM083864 · NIGMS · WASHINGTON STATE UNIVERSITY · PI NILSON, JOHN H. · 2010 to 2014
$646k
NICHD NIH HHS R01 HD065859NIGMS NIH HHS T32 GM083864
6 · The paper itself

Abstract

Within the ovarian follicle, granulosa cells (GCs) surround and support immature oocytes. FSH promotes the differentiation and proliferation of GCs and is essential for fertility. We recently reported that ERK activation is necessary for FSH to induce key genes that define the preovulatory GC. This research focused on the phosphoregulation by FSH of ERK within GCs. FSH-stimulated ERK phosphorylation on Thr(202)/Tyr(204) was PKA-dependent, but MEK(Ser(217)/Ser(221)) phosphorylation was not regulated; rather, MEK was already active. However, treatment of GCs with the EGF receptor inhibitor AG1478, a dominant-negative RAS, an Src homology 2 domain-containing Tyr phosphatase inhibitor (NSC 87877), or the MEK inhibitor PD98059 blocked FSH-dependent ERK(Thr(202)/Tyr(204)) phosphorylation, demonstrating the requirement for upstream pathway components. We hypothesized that FSH via PKA enhances ERK phosphorylation by inhibiting the activity of a protein phosphatase that constitutively dephosphorylates ERK in the absence of FSH, allowing MEK-phosphorylated ERK to accumulate in the presence of FSH because of inactivation of the phosphatase. GCs treated with different phosphatase inhibitors permitted elimination of both Ser/Thr and Tyr phosphatases and implicated dual specificity phosphatases (DUSPs) in the dephosphorylation of ERK. Treatment with MAP kinase phosphatase (MKP3, DUSP6) inhibitors increased ERK(Thr(202)/Tyr(204)) phosphorylation in the absence of FSH to levels comparable with ERK phosphorylated in the presence of FSH. ERK co-immunoprecipitated with Myc-FLAG-tagged MKP3(DUSP6). GCs treated with MKP3(DUSP6) inhibitors blocked and PKA inhibitors enhanced dephosphorylation of recombinant ERK2-GST in an in vitro phosphatase assay. Together, these results suggest that FSH-stimulated ERK activation in GCs requires the PKA-dependent inactivation of MKP3(DUSP6).

Indexed as

AnimalsCyclic AMP-Dependent Protein KinasesDual Specificity Phosphatase 6Extracellular Signal-Regulated MAP KinasesFemaleFlavonoidsFollicle Stimulating HormoneGranulosa CellsPhosphorylationProtein Kinase InhibitorsRatsRats, Sprague-Dawley2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-oneCyclic AMP-Dependent Protein KinasesDual Specificity Phosphatase 6Dusp6 protein, ratExtracellular Signal-Regulated MAP KinasesFlavonoidsFollicle Stimulating HormoneProtein Kinase Inhibitorsdual specificity phosphatase 6 (DUSP6)dual specificity phosphoprotein phosphataseERKFSHgene expressiongranulosa cellsMAP kinase phosphatase 3 (MKP3)ovaryPKA

Identifiers

PMID27422819
PMCPMC5016702
OpenAlexW2515256877

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.