Evidence map›Paper›PMID 23335370›Full record

ArticleBlood2013

The Rac GTPase effector p21-activated kinase is essential for hematopoietic stem/progenitor cell migration and engraftment.

Adrienne M Dorrance, Serena De Vita, Maria Radu, Pavankumar N G Reddy, Meaghan K McGuinness, Chad E Harris, Ronald Mathieu, Steven W Lane, Rachelle Kosoff, Michael D Milsom and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

25 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
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  10. Prognostic and biological significance of the proangiogenic factor EGFL7 in acute myeloid leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  11. Article
  12. Article
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  17. Beta-Chemokine CCL15 Affects the Adhesion and Migration of Hematopoietic Progenitor Cells.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2015
    Article
  18. Review
  19. 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

12 authors at 3 institutions in 1 country.

Adrienne M DorranceDivision of Hematology/Oncology, Children's Hospital Boston, Boston, MA 02115, USA.
Serena De Vita
Maria Radu
Pavankumar N G Reddy
Meaghan K McGuinness
Chad E Harris
Ronald Mathieu
Steven W Lane
Rachelle Kosoff
Michael D Milsom
Jonathan Chernoff
David A Williams
Boston Children's Hospital · USFox Chase Cancer Center · USThe Ohio State University · US

Funding

PATHOPHYSIOLOGY OF HUMAN BLOOD CELLST32HL007574 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI Daniel Evan Bauer · 1985 to 2026
$18.4M
CORE--ZEBRAFISHP30DK049216 · NIDDK · CHILDREN'S HOSPITAL BOSTON · PI ORKIN, STUART H · 1999 to 2015
$14.3M
TRAINING PROGRAM IN CANCER RESEARCHT32CA009035 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI CHERNOFF, JONATHAN · 1985 to 2020
$10.5M
TRANSFUSION BIOLOGY AND MEDICINET32HL066987 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI JOHN P MANIS · 2001 to 2026
$10.2M
Rac proteins in hematopoietic cell survival and functionR01DK062757 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI WILLIAMS, DAVID A · 2002 to 2016
$5.7M
Targeting the Kinome in Neurofibromatosis type 1R01CA142928 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI CHERNOFF, JONATHAN · 2010 to 2019
$3.9M
Signaling by p21-activated protein kinasesR01CA117884 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI CHERNOFF, JONATHAN · 2006 to 2010
$1.8M
NCI NIH HHS R01 CA117884NCI NIH HHS R01CA117884-2NCI NIH HHS R01 CA142928NCI NIH HHS R01CA142928-3NCI NIH HHS T32 CA009035NHLBI NIH HHS 5 T32 HL 007574-29NHLBI NIH HHS 5 T32 HL066987-08NHLBI NIH HHS T32 HL007574NHLBI NIH HHS T32 HL066987NIDDK NIH HHS 5R01DK062757-11NIDDK NIH HHS P30 DK049216NIDDK NIH HHS R01 DK062757
6 · The paper itself

Abstract

The p21-activated kinases (Paks) are serine/threonine kinases that are major effectors of the Rho guanosine 5'\x{2011}triphosphatase, Rac, and Cdc42. Rac and Cdc42 are known regulators of hematopoietic stem and progenitor cell (HSPC) function, however, a direct role for Paks in HSPCs has yet to be elucidated. Lin(-)Sca1(+)c-kit(+) (LSK) cells from wild-type mice were transduced with retrovirus expressing Pak inhibitory domain (PID), a well-characterized inhibitor of Pak activation. Defects in marrow homing and in vitro cell migration, assembly of the actin cytoskeleton, proliferation, and survival were associated with engraftment failure of PID-LSK. The PID-LSK demonstrated decreased phosphorylation of extracellular signal-regulated kinase (ERK), whereas constitutive activation of ERK in these cells led to rescue of hematopoietic progenitor cell proliferation in vitro and partial rescue of Pak-deficient HSPC homing and engraftment in vivo. Using conditional knock-out mice, we demonstrate that among group A Paks, Pak2(-/-) HSPC show reduced homing to the bone marrow and altered cell shape similar to PID-LSK cells in vitro and are completely defective in HSPC engraftment. These data demonstrate that Pak proteins are key components of multiple engraftment-associated HSPC functions and play a direct role in activation of ERK in HSPCs, and that Pak2 is specifically essential for HSPC engraftment.

Indexed as

Hematopoietic Stem Cell TransplantationAnimalsCell MovementCell ProliferationCells, CulturedCell SurvivalExtracellular Signal-Regulated MAP KinasesHematopoietic Stem CellsMiceMice, Inbred C57BLMice, Inbred NODMice, KnockoutMice, SCIDp21-Activated Kinasesrac GTP-Binding ProteinsExtracellular Signal-Regulated MAP Kinasesp21-Activated Kinasesrac GTP-Binding Proteins

Identifiers

PMID23335370
PMCPMC3612857
OpenAlexW1964653803

What OpenQuestion holds

Textmetadata
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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.