Evidence map›Paper›PMID 22509308›Full record

ArticlePloS one2012

Erythropoietin receptor signaling is membrane raft dependent.

Kathy L McGraw, Gwenny M Fuhler, Joseph O Johnson, Justine A Clark, Gisela C Caceres, Lubomir Sokol, Alan F List

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 24% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. STAT5 as a Key Protein of Erythropoietin Signalization.International journal of molecular sciences · 2021
    Review
  8. Review
  9. Review
  10. Article
  11. 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

7 authors at 2 institutions in 2 countries.

Kathy L McGrawDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, Florida, United States of America.
Gwenny M Fuhler
Joseph O Johnson
Justine A Clark
Gisela C Caceres
Lubomir Sokol
Alan F List
Moffitt Cancer Center · USErasmus MC · NL

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI KENNETH Lynn WRIGHT · 1998 to 2026
$93.5M
Phosphatase Targets of Lenalidomide in Myelodysplastic SyndromeR01CA131076 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI LIST, ALAN F · 2008 to 2012
$2.2M
NCI NIH HHS 5R01CA13107604NCI NIH HHS P30 CA076292NCI NIH HHS R01 CA131076
6 · The paper itself

Abstract

Upon erythropoietin (Epo) engagement, Epo-receptor (R) homodimerizes to activate JAK2 and Lyn, which phosphorylate STAT5. Although recent investigations have identified key negative regulators of Epo-R signaling, little is known about the role of membrane localization in controlling receptor signal fidelity. Here we show a critical role for membrane raft (MR) microdomains in creation of discrete signaling platforms essential for Epo-R signaling. Treatment of UT7 cells with Epo induced MR assembly and coalescence. Confocal microscopy showed that raft aggregates significantly increased after Epo stimulation (mean, 4.3±1.4(SE) vs. 25.6±3.2 aggregates/cell; p≤0.001), accompanied by a >3-fold increase in cluster size (p≤0.001). Raft fraction immunoblotting showed Epo-R translocation to MR after Epo stimulation and was confirmed by fluorescence microscopy in Epo stimulated UT7 cells and primary erythroid bursts. Receptor recruitment into MR was accompanied by incorporation of JAK2, Lyn, and STAT5 and their activated forms. Raft disruption by cholesterol depletion extinguished Epo induced Jak2, STAT5, Akt and MAPK phosphorylation in UT7 cells and erythroid progenitors. Furthermore, inhibition of the Rho GTPases Rac1 or RhoA blocked receptor recruitment into raft fractions, indicating a role for these GTPases in receptor trafficking. These data establish a critical role for MR in recruitment and assembly of Epo-R and signal intermediates into discrete membrane signaling units.

Indexed as

Signal TransductionAnimalsCell Line, TumorEnzyme InhibitorsErythroid Precursor CellsHumansMembrane MicrodomainsPhosphoproteinsProtein Transportrac1 GTP-Binding ProteinReceptors, ErythropoietinrhoA GTP-Binding ProteinSTAT5 Transcription FactorEnzyme InhibitorsPhosphoproteinsrac1 GTP-Binding ProteinReceptors, ErythropoietinrhoA GTP-Binding ProteinSTAT5 Transcription Factor

Identifiers

PMID22509308
PMCPMC3317978
OpenAlexW2036159060

What OpenQuestion holds

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LicenceCC BY
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.