Evidence map›Paper›PMID 19805221›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2009

Phosphorylation of WASp is a key regulator of activity and stability in vivo.

Michael P Blundell, Gerben Bouma, Joao Metelo, Austen Worth, Yolanda Calle, Lucy A Cowell, Lisa S Westerberg, Dale A Moulding, Samuel Mirando, Christine Kinnon and 5 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.3field-weighted citation impact, top 13% 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

35 citing papers in PubMed, 60 citations in OpenAlex.

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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

15 authors at 7 institutions in 3 countries.

Michael P BlundellMolecular Immunology Unit, Wolfson Centre for Gene Therapy of Childhood Disease and Centre for Immunodeficiency, UCL Institute of Child Health, London, WC1N 1EH, United Kingdom.
Gerben Bouma
Joao Metelo
Austen Worth
Yolanda Calle
Lucy A Cowell
Lisa S Westerberg
Dale A Moulding
Samuel Mirando
Christine Kinnon
Giles O Cory
Gareth E Jones
Scott B Snapper
Siobhan O Burns
Adrian J Thrasher
Great Ormond Street Hospital · GBUniversity College London · GBHarvard University · USKing's College London · GBKing's College School · GBMassachusetts General Hospital · USPeninsula College of Medicine and Dentistry · GB

Funding

Medical Research Council G0401026Wellcome Trust 080373
6 · The paper itself

Abstract

The Wiskott-Aldrich syndrome protein (WASp) is a key cytoskeletal regulator in hematopoietic cells. Covalent modification of a conserved tyrosine by phosphorylation has emerged as an important potential determinant of activity, although the physiological significance remains uncertain. In a murine knockin model, mutation resulting in inability to phosphorylate Y293 (Y293F) mimicked many features of complete WASp-deficiency. Although a phosphomimicking mutant Y293E conferred enhanced actin-polymerization, the cellular phenotype was similar due to functional dysregulation. Furthermore, steady-state levels of Y293E-WASp were markedly reduced compared to wild-type WASp and Y293F-WASp, although partially recoverable by treatment of cells with proteasome inhibitors. Consequently, tyrosine phosphorylation plays a critical role in normal activation of WASp in vivo, and is indispensible for multiple tasks including proliferation, phagocytosis, chemotaxis, and assembly of adhesion structures. Furthermore, it may target WASp for proteasome-mediated degradation, thereby providing a default mechanism for self-limiting stimulation of the Arp2/3 complex.

Indexed as

ActinsAmino Acid SubstitutionAnimalsBinding SitesCell LineCell MovementChlorocebus aethiopsCOS CellsHematopoiesisHumansIn Vitro TechniquesMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMutagenesis, Site-DirectedActinsRecombinant ProteinsTyrosineWas protein, mouseWiskott-Aldrich Syndrome Protein

Identifiers

PMID19805221
PMCPMC2736139
OpenAlexW2061900998

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.