Evidence map›Paper›PMID 17925492›Full record

ArticleBlood2008

Roles of focal adhesion kinase (FAK) in megakaryopoiesis and platelet function: studies using a megakaryocyte lineage specific FAK knockout.

Ian S Hitchcock, Norma E Fox, Nicolas Prévost, Katherine Sear, Sanford J Shattil, Kenneth Kaushansky

Open access · greenAbstract read
In one paragraph

Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

54 citing papers in PubMed, 86 citations in OpenAlex.

  1. Article
  2. Review
  3. Platelet spreading and clot retraction are regulated by 2 distinct αThe Journal of pharmacology and experimental therapeutics · 2025
    Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. FAK Family Kinases in Vascular Diseases.International journal of molecular sciences · 2020
    Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Integrin αBlood · 2017
    Review
  17. Article
  18. Haematologica · 2017
    Article
  19. Article
  20. 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

6 authors at 1 institution in 1 country.

Ian S HitchcockDepartment of Medicine, University of California San Diego, La Jolla 92093, USA.
Norma E Fox
Nicolas Prévost
Katherine Sear
Sanford J Shattil
Kenneth Kaushansky
University of California, San Diego · US

Funding

The Interaction of TPO and Integrins in Hematopoiesis CellsP01HL078784 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GINSBERG, MARK HOWARD · 2005 to 2019
$28.3M
TYROSINE KINASE C-ABL AND BCR-ABL IN INTEGRIN DEPENDENT SIGNALINGP01HL057900 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHATTIL, SANFORD J · 1997 to 2012
$17.4M
MOLECULAR AND CELLULAR BIOLOGY OF THROMBOPOIETINR01DK049855 · NIDDK · UNIVERSITY OF WASHINGTON · PI GEDDIS, AMY E, KAUSHANSKY, KENNETH · 1995 to 2013
$5.0M
NHLBI NIH HHS HL57900NHLBI NIH HHS HL78784NHLBI NIH HHS P01 HL057900NHLBI NIH HHS P01 HL078784NHLBI NIH HHS P01 HL078784-04NIDDK NIH HHS R01 DK049855NIDDK NIH HHS R01DK49855
6 · The paper itself

Abstract

Focal adhesion kinase (FAK) plays a key role in mediating signaling downstream of integrins and growth factor receptors. In this study, we determined the roles of FAK in vivo by generating a megakaryocyte lineage-specific FAK-null mouse (Pf4-Cre/FAK-floxed). Megakaryocyte and platelet FAK expression was ablated in Pf4-Cre/FAK-floxed mice without affecting expression of the FAK homologue PYK2, although PYK2 phosphorylation was increased in FAK-/- megakaryocytes in response to fibrinogen. Megakaryopoiesis is greatly enhanced in Pf4-Cre/FAK-floxed mice, with significant increases in megakaryocytic progenitors (CFU-MK), mature megakaryocytes, megakaryocyte ploidy, and moderate increases in resting platelet number and platelet recovery following a thrombocytopenic stress. Thrombopoietin (Tpo)-mediated activation of Lyn kinase, a negative regulator of megakaryopoiesis, is severely attenuated in FAK-null megakaryocytes compared with wild-type controls. In contrast, Tpo-mediated activation of positive megakaryopoiesis regulators such as ERK1/2 and AKT is increased in FAK-null megakaryocytes, providing a plausible explanation for the observed increases in megakaryopoiesis in these mice. In Pf4-Cre/FAK-floxed mice, rebleeding times are significantly increased, and FAK-null platelets exhibit diminished spreading on immobilized fibrinogen. These studies establish clear roles for FAK in megakaryocyte growth and platelet function, setting the stage for manipulation of this component of the Tpo signaling apparatus for therapeutic benefit.

Indexed as

AnimalsBlood PlateletsFocal Adhesion Kinase 1Gene Expression Regulation, EnzymologicMAP Kinase Signaling SystemMegakaryocytesMiceMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3PloidiesProto-Oncogene Proteins c-aktThrombocytopeniaThrombopoiesisThrombopoietinFocal Adhesion Kinase 1Mitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Proto-Oncogene Proteins c-aktPtk2 protein, mouseThrombopoietin

Identifiers

PMID17925492
PMCPMC2200856
OpenAlexW1968821921

What OpenQuestion holds

Textmetadata
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.