Evidence map›Paper›PMID 25824689›Full record

ArticleBlood2015

Pak2 restrains endomitosis during megakaryopoiesis and alters cytoskeleton organization.

Rachelle E Kosoff, Joseph E Aslan, John C Kostyak, Essel Dulaimi, Hoi Yee Chow, Tatiana Y Prudnikova, Maria Radu, Satya P Kunapuli, Owen J T McCarty, Jonathan Chernoff

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.2field-weighted citation impact, top 6% 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

28 citing papers in PubMed, 53 citations in OpenAlex.

  1. PAK2-driven cytoskeleton-endosome dynamics control macrophage hyperphagia and SIRPA engagement.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  10. Pak2 reduction induces a failure of early embryonic development in mice.Reproductive biology and endocrinology : RB&E · 2021
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  16. New insights into cytoskeletal remodeling during platelet production.Journal of thrombosis and haemostasis : JTH · 2019
    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

10 authors at 3 institutions in 1 country.

Rachelle E KosoffCancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA; Cell and Molecular Biology, University of Pennsylvania School of Medicine, Philadelphia, PA;
Joseph E AslanDepartment of Biomedical Engineering, Oregon Health and Science University, Portland, OR;ORCID http://orcid.org/0000-0002-8873-0387
John C KostyakSol Sherry Thrombosis Research Center, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA; and.
Essel DulaimiDepartment of Pathology, Fox Chase Cancer Center, Philadelphia, PA.
Hoi Yee ChowCancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA;
Tatiana Y PrudnikovaCancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA;
Maria RaduCancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA;
Satya P KunapuliSol Sherry Thrombosis Research Center, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA; and.
Owen J T McCartyDepartment of Biomedical Engineering, Oregon Health and Science University, Portland, OR;ORCID http://orcid.org/0000-0001-9481-0124
Jonathan ChernoffCancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA;ORCID http://orcid.org/0000-0002-4803-7836
Fox Chase Cancer Center · USOregon Health & Science University · USTemple University · US

Funding

WORD PROCESSING CENTER--COREP30CA006927 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Dietmar J Kappes · 1985 to 2026
$138.8M
TRAINING PROGRAM IN CANCER RESEARCHT32CA009035 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI CHERNOFF, JONATHAN · 1985 to 2020
$10.5M
Characterization of Coagulation Factor-platelet Interactions: Role of FXIR01HL101972 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Owen J McCarty · 2010 to 2026
$8.5M
The Role of p21-Activated Kinases in Malignant MesotheliomaR01CA148805 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI CHERNOFF, JONATHAN, TESTA, JOSEPH R. · 2011 to 2020
$4.0M
Targeting the Kinome in Neurofibromatosis type 1R01CA142928 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI CHERNOFF, JONATHAN · 2010 to 2019
$3.9M
Functional PKC Isoforms in PlateletsR01HL093231 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI KUNAPULI, SATYA P. · 2009 to 2017
$3.6M
Regulation and function of PDK1-Akt-Pyk2 axis in plateletsR01HL118593 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI KUNAPULI, SATYA P. · 2013 to 2016
$1.9M
P21-activated kinase 1 and 2 as therapeutic targets of the NF1 microenvironmentF31CA177182 · NCI · UNIVERSITY OF PENNSYLVANIA · PI KOSOFF, RACHELLE · 2013 to 2013
$29k
NCI NIH HHS F31 CA177182NCI NIH HHS F31-CA177182NCI NIH HHS P30 CA006927NCI NIH HHS P30-CA006927NCI NIH HHS R01 CA142928NCI NIH HHS R01-CA142928NCI NIH HHS R01 CA148805NCI NIH HHS R01-CA148805NCI NIH HHS T32 CA009035NHLBI NIH HHS R01 HL093231NHLBI NIH HHS R01 HL101972NHLBI NIH HHS R01-HL101972NHLBI NIH HHS R01 HL118593NHLBI NIH HHS R01-HL118593NHLBI NIH HHS R01-HL93231
6 · The paper itself

Abstract

Megakaryocyte maturation and polyploidization are critical for platelet production; abnormalities in these processes are associated with myeloproliferative disorders, including thrombocytopenia. Megakaryocyte maturation signals through cascades that involve p21-activated kinase (Pak) function; however, the specific role for Pak kinases in megakaryocyte biology remains elusive. Here, we identify Pak2 as an essential effector of megakaryocyte maturation, polyploidization, and proplatelet formation. Genetic deletion of Pak2 in murine bone marrow is associated with macrothrombocytopenia, altered megakaryocyte ultrastructure, increased bone marrow megakaryocyte precursors, and an elevation of mature CD41(+) megakaryocytes, as well as an increased number of polyploid cells. In Pak2(-/-) mice, platelet clearance rate was increased, as was production of newly synthesized, reticulated platelets. In vitro, Pak2(-/-) megakaryocytes demonstrate increased polyploidization associated with alterations in β1-tubulin expression and organization, decreased proplatelet extensions, and reduced phosphorylation of the endomitosis regulators LIM domain kinase 1, cofilin, and Aurora A/B/C. Together, these data establish a novel role for Pak2 as an important regulator of megakaryopoiesis, polyploidization, and cytoskeletal dynamics in developing megakaryocytes.

Indexed as

AnimalsBlood PlateletsBone MarrowCytoskeletonMegakaryocytesMiceMice, Inbred C57BLMice, KnockoutMice, SCIDMicroscopy, FluorescenceMitosisPAX2 Transcription FactorPolyploidyStem CellsThrombocytopeniaThrombopoiesisPax2 protein, mousePAX2 Transcription Factor

Identifiers

PMID25824689
PMCPMC4424419
OpenAlexW2014616046

What OpenQuestion holds

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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.