Evidence map›Paper›PMID 25492869›Full record

ArticleThe Journal of biological chemistry2015

Phosphorylation of ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) by Akt promotes stability and mitogenic function of S-phase kinase-associated protein-2 (Skp2).

Gyun Jee Song, Kristen L Leslie, Stacey Barrick, Tatyana Mamonova, Jeremy M Fitzpatrick, Kenneth W Drombosky, Noah Peyser, Bin Wang, Maria Pellegrini, Philip M Bauer and 3 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.7field-weighted citation impact, top 29% 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

11 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
  2. Article
  3. Cotranslational interaction of human EBP50 and ezrin overcomes masked binding site during complex assembly.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  4. A Critical Role for NaJournal of immunology (Baltimore, Md. : 1950) · 2021
    Article
  5. Article
  6. Article
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  10. Review
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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

13 authors at 4 institutions in 2 countries.

Gyun Jee SongFrom the Department of Pharmacology and Chemical Biology, Department of Pharmacology, Brain Science and Engineering Institute, School of Medicine, Kungpook National University, Daegu 702-701, Korea, and.
Kristen L LeslieFrom the Department of Pharmacology and Chemical Biology.
Stacey BarrickFrom the Department of Pharmacology and Chemical Biology.
Tatyana MamonovaFrom the Department of Pharmacology and Chemical Biology.
Jeremy M FitzpatrickDepartment of Chemistry, Dartmouth College, Hanover, New Hampshire 03755.
Kenneth W DromboskyFrom the Department of Pharmacology and Chemical Biology.
Noah PeyserFrom the Department of Pharmacology and Chemical Biology.
Bin WangFrom the Department of Pharmacology and Chemical Biology.
Maria PellegriniDepartment of Chemistry, Dartmouth College, Hanover, New Hampshire 03755.
Philip M BauerVascular Medicine Institute, and Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260.
Peter A FriedmanFrom the Department of Pharmacology and Chemical Biology.
Dale F MierkeDepartment of Chemistry, Dartmouth College, Hanover, New Hampshire 03755.
Alessandro BiselloFrom the Department of Pharmacology and Chemical Biology, Vascular Medicine Institute, and alb138@pitt.edu.
Dartmouth College · USKyungpook National University · KRReproductive Medicine Institute · USUniversity of Pittsburgh · US

Funding

UNIVERSITY OF PITTSBURGH CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE: BPCAUL1RR024153 · NCRR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2006 to 2011
$73.9M
University of Pittsburgh Clinical and Translational Science InstituteUL1TR000005 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2012 to 2015
$50.8M
EBP50 REGULATION OF PTH RECEPTOR IN BONE AND KIDNEYR01DK069998 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FRIEDMAN, PETER A · 2006 to 2014
$2.9M
NCATS NIH HHS UL1 TR000005NCATS NIH HHS UL1TR000005NCRR NIH HHS S10 RR-025085NCRR NIH HHS UL1 RR024153NIDDK NIH HHS R01 DK069998NIDDK NIH HHS R01-DK069998
6 · The paper itself

Abstract

The regulation of the cell cycle by the ubiquitin-proteasome system is dependent on the activity of E3 ligases. Skp2 (S-phase kinase associated protein-2) is the substrate recognition subunit of the E3 ligase that ubiquitylates the cell cycle inhibitors p21(cip1) and p27(kip1) thus promoting cell cycle progression. Increased expression of Skp2 is frequently observed in diseases characterized by excessive cell proliferation, such as cancer and neointima hyperplasia. The stability and cellular localization of Skp2 are regulated by Akt, but the molecular mechanisms underlying these effects remain only partly understood. The scaffolding protein Ezrin-Binding Phosphoprotein of 50 kDa (EBP50) contains two PDZ domains and plays a critical role in the development of neointimal hyperplasia. Here we report that EBP50 directly binds Skp2 via its first PDZ domain. Moreover, EBP50 is phosphorylated by Akt on Thr-156 within the second PDZ domain, an event that allosterically promotes binding to Skp2. The interaction with EBP50 causes cytoplasmic localization of Skp2, increases Skp2 stability and promotes proliferation of primary vascular smooth muscle cells. Collectively, these studies define a novel regulatory mechanism contributing to aberrant cell growth and highlight the importance of scaffolding function of EBP50 in Akt-dependent cell proliferation.

Indexed as

AnimalsCell ProliferationCells, CulturedHumansMicePhosphoproteinsPhosphorylationProtein BindingProtein StabilityProto-Oncogene Proteins c-aktSodium-Hydrogen ExchangersS-Phase Kinase-Associated ProteinsPhosphoproteinsProto-Oncogene Proteins c-aktsodium-hydrogen exchanger regulatory factorSodium-Hydrogen ExchangersS-Phase Kinase-Associated ProteinsAkt PKBCell ProliferationEBP50nherfnherf1PDZ DomainPhosphorylationSkp2Vascular Smooth Muscle Cells

Identifiers

PMID25492869
PMCPMC4317011
OpenAlexW2117897243

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.