Evidence map›Paper›PMID 14662339›Full record

ArticleExperimental hematology2003

Hematopoietic cell survival signals are elicited through non-tyrosine-containing sequences in the membrane-proximal region of the erythropoietin receptor (EPOR) by a Stat5-dependent pathway.

Donghoon Yoon, Stephanie S Watowich

Abstract read
In one paragraph

Article in Experimental hematology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.4field-weighted citation impact, top 41% 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

6 citing papers in PubMed, 14 citations in OpenAlex.

  1. STAT5 as a Key Protein of Erythropoietin Signalization.International journal of molecular sciences · 2021
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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

2 authors at 1 institution in 1 country.

Donghoon YoonDepartment of Immunology, The University of Texas MD Anderson Cancer Center, and Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
Stephanie S Watowich
The University of Texas MD Anderson Cancer Center · US

Funding

MOLECULAR MECHANISMS CYTOKINE RECEPTOR SIGNALINGR01CA077447 · NCI · UNIVERSITY OF TEXAS MD ANDERSON CAN CTR · PI WATOWICH, STEPHANIE S · 1998 to 2000
$250k
NCI NIH HHS CA 77447NCI NIH HHS R01 CA077447
6 · The paper itself

Abstract

objectiveErythropoietin is essential for red blood cell development in vivo and is also an important therapeutic agent to treat anemia resulting from kidney failure or bone marrow suppression. The erythropoietin receptor (EPOR) elicits both positive and negative regulatory signaling pathways, primarily through phosphorylated tyrosine residues in the cytoplasmic domain of the activated receptor complex. Surprisingly, however, EPOR tyrosine residues are dispensable for in vivo erythropoiesis under nonstress conditions. One of the key signaling molecules elicited by the EPOR is the Stat5 transcription factor. Stat5 activation has been mapped to tyrosines 343 and 401 in the EPOR cytoplasmic region, although non-tyrosine-containing sequences in the EPOR cytoplasmic region can also stimulate Stat5. To test the functional role of non-tyrosine-containing sequences in the EPOR, we analyzed a series of mutant EPOR isoforms in cell survival and proliferation assays.

methodsThe IL-3-dependent 32D cell line was stably transfected with cDNAs encoding the wild-type EPOR or mutant EPORs containing or lacking intracellular tyrosines, in the absence or presence of a dominant inhibitory Stat5 isoform. EPO-dependent cell signaling, survival, and proliferation were evaluated.

resultsEPOR isoforms lacking intracellular tyrosine residues elicit an important survival signal in 32D cells. Stat5 function is critical for EPO-dependent cell survival mediated by these non-tyrosine-containing receptor sequences. Interestingly, EPO-dependent survival does not require the presence of fetal calf serum (FCS) in the culture medium, yet FCS is important for 32D cell proliferation in response to EPO.

conclusionOur results elucidate a previously unrecognized survival pathway elicited by the EPOR. They demonstrate that this pathway requires Stat5 and is serum independent. These findings contribute significantly to our understanding of the complexity by which the EPOR functions in hematopoietic cells.

Indexed as

Milk ProteinsSignal TransductionAmino Acid SequenceAnimalsCell DivisionCell SurvivalDNA-Binding ProteinsHematopoietic Stem CellsMiceMutagenesis, Site-DirectedReceptors, ErythropoietinSTAT5 Transcription FactorTrans-ActivatorsTransfectionTyrosineDNA-Binding ProteinsMilk ProteinsReceptors, ErythropoietinSTAT5 Transcription FactorTrans-ActivatorsTyrosine

Identifiers

PMID14662339
PMCPMC2388246
OpenAlexW1969697378

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.