Evidence map›Paper›PMID 25171405›Full record

ArticleCell2014

A secreted tyrosine kinase acts in the extracellular environment.

Mattia R Bordoli, Jina Yum, Susanne B Breitkopf, Jonathan N Thon, Joseph E Italiano, Junyu Xiao, Carolyn Worby, Swee-Kee Wong, Grace Lin, Maja Edenius and 5 more

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 84 papers.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

84 citing papers in PubMed, 123 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Mechanisms of assembly and remodelling of the extracellular matrix.Nature reviews. Molecular cell biology · 2024
    Review
  8. Article
  9. Article
  10. Article
  11. A commoneLife · 2024
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Promotion of Lung Cancer Metastasis by SIRT2-Mediated Extracellular Protein Deacetylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 2 countries.

Mattia R BordoliDepartment of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.
Jina YumDepartment of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA; Department of Life Science and Global Top5 Research Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
Susanne B BreitkopfDivision of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Jonathan N ThonDepartment of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
Joseph E ItalianoDepartment of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Vascular Biology Program, Department of Surgery, Children's Hospital, Boston, MA 02115, USA.
Junyu XiaoDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92031, USA.
Carolyn WorbyDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92031, USA.
Swee-Kee WongDepartment of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.
Grace LinDepartment of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.
Maja EdeniusDepartment of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.
Tracy L KellerDepartment of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.
John M AsaraDivision of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Jack E DixonDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92031, USA.
Chang-Yeol YeoDepartment of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA; Department of Life Science and Global Top5 Research Program, Ewha Womans University, Seoul 120-750, Republic of Korea. Electronic address: cyeo@ewha.ac.kr.
Malcolm WhitmanDepartment of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA. Electronic address: mwhitman@hms.harvard.edu.
Harvard University · USUniversity of California, San Diego · USBeth Israel Deaconess Medical Center · USBrigham and Women's Hospital · USEwha Womans University · KR

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI Deborah J Goff · 1985 to 2026
$330.6M
Tuberous Sclerosis-Pathway and PathogenesisP01CA120964 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI David J. Kwiatkowski · 2007 to 2026
$35.9M
Cytoskeletal Mechanisms of Platelet FormationR01HL068130 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI ITALIANO, JOSEPH E · 2001 to 2021
$8.1M
REGULATION OF NEUROPEPTIDE BIOSYNTHESISR01DK018849 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DIXON, JACK E, WORBY, CAROLYN ANN · 1986 to 2020
$7.0M
STUDIES ON PANCREATIC HORMONESR37DK018024 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DIXON, JACK E · 1988 to 2013
$5.6M
STUDIES ON PANCREATIC HORMONESR01DK018024 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIXON, JACK E, WORBY, CAROLYN ANN · 1986 to 2018
$2.1M
MECHANISM OF ACTION OF HALOFUGINONE AS A NOVEL THERAPEUTICR01GM089885 · NIGMS · HARVARD MEDICAL SCHOOL · PI WHITMAN, MALCOLM R. · 2010 to 2013
$1.5M
Role of a Novel Secreted Protein Tyrosine Kinase in DevelopmentR21DE024312 · NIDCR · HARVARD MEDICAL SCHOOL · PI WHITMAN, MALCOLM R. · 2014 to 2015
$618k
High Resolution Mass Spectrometry SystemS10OD010612 · OD · BETH ISRAEL DEACONESS MEDICAL CENTER · PI ASARA, JOHN M · 2012 to 2012
$600k
Examination of the Final Stages of Platelet ProductionK99HL114719 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI THON, JONATHAN N · 2013 to 2014
$266k
NCI NIH HHS 5P01CA120964NCI NIH HHS 5P30CA006516NCI NIH HHS P01 CA120964NCI NIH HHS P30 CA006516NHLBI NIH HHS 1K99HL114719-01A1NHLBI NIH HHS HL68130NHLBI NIH HHS K99 HL114719NHLBI NIH HHS R01 HL068130NIDCR NIH HHS DE024312NIDCR NIH HHS R21 DE024312NIDDK NIH HHS DK 18024NIDDK NIH HHS DK 18849NIDDK NIH HHS R01 DK018024NIDDK NIH HHS R01 DK018849NIDDK NIH HHS R37 DK018024NIGMS NIH HHS GM089885NIGMS NIH HHS R01 GM089885NIH HHS 1S10OD010612NIH HHS S10 OD010612
6 · The paper itself

Abstract

Although tyrosine phosphorylation of extracellular proteins has been reported to occur extensively in vivo, no secreted protein tyrosine kinase has been identified. As a result, investigation of the potential role of extracellular tyrosine phosphorylation in physiological and pathological tissue regulation has not been possible. Here, we show that VLK, a putative protein kinase previously shown to be essential in embryonic development, is a secreted protein kinase, with preference for tyrosine, that phosphorylates a broad range of secreted and ER-resident substrate proteins. We find that VLK is rapidly and quantitatively secreted from platelets in response to stimuli and can tyrosine phosphorylate coreleased proteins utilizing endogenous as well as exogenous ATP sources. We propose that discovery of VLK activity provides an explanation for the extensive and conserved pattern of extracellular tyrosine phosphophorylation seen in vivo, and extends the importance of regulated tyrosine phosphorylation into the extracellular environment.

Indexed as

Amino Acid SequenceAnimalsBlood PlateletsEmbryo, MammalianEmbryonic DevelopmentGlycosylationHumansMiceMolecular Sequence DataPhosphorylationProtein KinasesProtein Processing, Post-TranslationalProtein Structure, TertiaryProtein-Tyrosine KinasesSecretory PathwayPKDCC protein, humanProtein KinasesProtein-Tyrosine KinasesVlk protein, mouse

Identifiers

PMID25171405
PMCPMC4149754
OpenAlexW2005042639

What OpenQuestion holds

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LicenceTDM
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.