Evidence map›Paper›PMID 15169891›Full record

ArticleMolecular and cellular biology2004

Erk/Src phosphorylation of cortactin acts as a switch on-switch off mechanism that controls its ability to activate N-WASP.

Narcisa Martinez-Quiles, Hsin-Yi Henry Ho, Marc W Kirschner, Narayanaswamy Ramesh, Raif S Geha

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers.

0numbers the graph read from it
0cells of the map it votes in
144citing papers in PubMed
7.5field-weighted citation impact, top 2% 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

144 citing papers in PubMed, 288 citations in OpenAlex.

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  10. Alterations in cytoskeletal and CaFrontiers in cardiovascular medicine · 2023
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  11. CaCell death & disease · 2022
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  14. Cortactin in Lung Cell Function and Disease.International journal of molecular sciences · 2022
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. ERK signaling for cell migration and invasion.Frontiers in molecular biosciences · 2022
    Review
  20. Review

84 more citing papers are in PubMed but not listed here.

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 2 institutions in 2 countries.

Narcisa Martinez-QuilesDivision of Immunology, Children's Hospital, Boston, MA 02115, USA.
Hsin-Yi Henry Ho
Marc W Kirschner
Narayanaswamy Ramesh
Raif S Geha
Children's Hospital · TNHarvard University · US

Funding

WIP in TCR signaling and actin reorganizationP01HL059561 · NHLBI · IMMUNE DISEASE INSTITUTE, INC. · PI GEHA, RAIF SALIM · 1997 to 2012
$21.8M
TRANSGENIC MODELS OF T CELL RECEPTOR IMMUNODEFICIENCIESP01AI035714 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI TERHORST, CORNELIS P · 1994 to 2007
$9.3M
NHLBI NIH HHS HL-59561NHLBI NIH HHS P01 HL059561NIAID NIH HHS AI35714NIAID NIH HHS P01 AI035714
6 · The paper itself

Abstract

The Arp2/3 complex can be independently activated to initiate actin polymerization by the VCA domain of WASP family members and by the acidic N-terminal and F-actin-binding repeat region of cortactin, which possesses a C-terminal SH3 domain. Cortactin is a target for phosphorylation by Src tyrosine kinases and by serine/threonine kinases that include Erk. Here we demonstrate that cortactin binds N-WASP and WASP via its SH3 domain, induces in vitro N-WASP-mediated actin polymerization, and colocalizes with N-WASP and WASP at sites of active actin polymerization. Erk phosphorylation and a mimicking S405,418D double mutation enhanced cortactin binding and activation of N-WASP. In contrast, Src phosphorylation inhibited the ability of cortactin previously phosphorylated by Erk, and that of S405,418D double mutant cortactin, to bind and activate N-WASP. Furthermore, Y-->D mutation of three tyrosine residues targeted by Src (Y421, Y466, and Y482) inhibited the ability of S405,418D cortactin to activate N-WASP. We propose that Erk phosphorylation liberates the SH3 domain of cortactin from intramolecular interactions with proline-rich regions, causing it to synergize with WASP and N-WASP in activating the Arp2/3 complex, and that Src phosphorylation terminates cortactin activation of N-WASP and WASP.

Indexed as

Actin-Related Protein 2Actin-Related Protein 3ActinsAnimalsBinding SitesCell LineCortactinCytoskeletal ProteinsHumansJurkat CellsMiceMicrofilament ProteinsMitogen-Activated Protein KinasesMutagenesis, Site-DirectedNerve Tissue ProteinsPhosphorylationActin-Related Protein 2Actin-Related Protein 3ActinsACTR2 protein, humanActr2 protein, mouseACTR3 protein, humanActr3 protein, mouseCortactinCTTN protein, humanCttn protein, mouseCytoskeletal ProteinsMicrofilament ProteinsMitogen-Activated Protein KinasesNerve Tissue ProteinsProteinsRecombinant Fusion Proteinssrc-Family KinasesWASL protein, humanWasl protein, mouseWAS protein, humanWas protein, mouseWiskott-Aldrich Syndrome ProteinWiskott-Aldrich Syndrome Protein, Neuronal

Identifiers

PMID15169891
PMCPMC419870
OpenAlexW2139130671

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.