Evidence map›Paper›PMID 19100679›Full record

ArticleExperimental hematology2009

A KIT juxtamembrane PY567 -directed pathway provides nonredundant signals for erythroid progenitor cell development and stress erythropoiesis.

Valter Agosti, Vinit Karur, Pradeep Sathyanarayana, Peter Besmer, Don M Wojchowski

Open access · bronzeAbstract read
In one paragraph

Article in Experimental hematology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

20 citing papers in PubMed, 34 citations in OpenAlex.

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  8. Direct engagement of the PI3K pathway by mutant KIT dominates oncogenic signaling in gastrointestinal stromal tumor.Proceedings of the National Academy of Sciences of the United States of America · 2017
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  20. Role of stem cell factor in the reactivation of human fetal hemoglobin.Mediterranean journal of hematology and infectious diseases · 2009
    Article
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

5 authors at 3 institutions in 2 countries.

Valter AgostiDevelopmental Biology Program, Sloan-Kettering Institute, New York, NY, USA.
Vinit Karur
Pradeep Sathyanarayana
Peter Besmer
Don M Wojchowski
Kettering University · USMaine Medical Center Research Institute · USMaine Medical Center · US

Funding

Transcriptional Decisions in Endothelial Cell DifferentiationP20RR015555 · NCRR · MAINE MEDICAL CENTER · PI PRUDOVSKY, IGOR · 2000 to 2009
$21.4M
WNT SIGNALING IN PREIMPLANTATION EMBRYOP20RR018789 · NCRR · MAINE MEDICAL CENTER · PI WOJCHOWSKI, DON MICHAEL · 2003 to 2011
$18.9M
IN VITRO STUDIES OF ERYTHROPOIETIN ACTIONR01HL044491 · NHLBI · UNIVERSITY OF NEW HAMPSHIRE · PI WOJCHOWSKI, DON MICHAEL · 1991 to 2020
$4.8M
PI 3-KINASE AND KIT RECEPTOR SIGNALINGR01HL055748 · NHLBI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI BESMER, PETER · 1997 to 2012
$4.0M
NCRR NIH HHS P20 RR015555NCRR NIH HHS P20-RR015555NCRR NIH HHS P20 RR018789NCRR NIH HHS P20-RR018789NHLBI NIH HHS R01 HL044491NHLBI NIH HHS R01 HL055748NHLBI NIH HHS R01-HL-4449NHLBI NIH HHS R01-HL-55748
6 · The paper itself

Abstract

objectiveKITL/KIT can elicit diverse sets of signals within lymphoid, myeloid, mast, and erythroid lineages, and exert distinct effects on growth, survival, migration, adhesion, and secretory responses. Presently, we have applied a PY-mutant allele knockin approach to specifically assess possible roles for KIT-PY567 and KIT-PY719 sites, and coupled pathways, during erythropoiesis. MATERIALS AND

methodsMouse models used to investigate this problem include those harboring knocked-in KIT(Y567F/Y567F), KIT(Y569F/Y569F), KIT(Y719F,Y719F), and KIT(Y567F/Y567F:Y569F/Y569F) alleles. The erythron was stressed by myelosuppression using 5-fluorouracil, and by phenylhydrazine-induced hemolysis. In addition, optimized systems for ex vivo analyses of bone marrow and splenic erythropoiesis were employed to more directly analyze possible stage-specific effects on erythroid cell growth, survival, development and KIT signaling events.

resultsIn Kit(Y567F/Y567F) mice, steady-state erythropoiesis was unperturbed while recovery from anemia due to 5-fluorouracil or phenylhydrazine was markedly impaired. Deficiencies in erythroid progenitor expansion occurred both in the bone marrow and the spleen. Responses to chronic erythropoietin dosing were also compromised. Ex vivo, Kit(Y567F/Y567F) (pro)erythroblast development was skewed from a Kit(pos)CD71(high) stage toward a subsequent Kit(neg)CD71(high) compartment. Proliferation and, to an extent, survival capacities were also compromised. Similar stage-specific defects existed for erythroid progenitors from Kit(Y567F/Y567F:Y569F/Y569F) but not KIT(Y719F/Y719F) mice. Kit(Y567F/Y567F) erythroblasts were used further to analyze KIT-PY567-dependent signals. MEK-1,2/ERK-1,2 signaling was unaffected while AKT, p70S6K, and especially JNK2/p54 pathways were selectively attenuated.

conclusionsNonredundant KIT-PY567-directed erythroblast-intrinsic signals are selectively critical for stress erythropoiesis. Investigations also add to an understanding of how KIT directs distinct outcomes among diverse progenitors and lineages.

Indexed as

ErythropoiesisMAP Kinase Signaling SystemAmino Acid SubstitutionAnemiaAnimalsAntimetabolites, AntineoplasticErythroid Precursor CellsFluorouracilHemolysisMiceMice, KnockoutMutation, MissenseOxidantsPhenylhydrazinesProtein KinasesProto-Oncogene Proteins c-kitAntimetabolites, AntineoplasticFluorouracilOxidantsphenylhydrazinePhenylhydrazinesProtein KinasesProto-Oncogene Proteins c-kitStem Cell Factor

Identifiers

PMID19100679
PMCPMC2701661
OpenAlexW1986828704

What Socratic holds

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Registered trials

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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 Socratic graph.