Evidence map›Paper›PMID 27601625›Full record

ArticleJournal of leukocyte biology2017

Selenoprotein K regulation of palmitoylation and calpain cleavage of ASAP2 is required for efficient FcγR-mediated phagocytosis.

Robert L Norton, Gregory J Fredericks, Zhi Huang, Jeffrey D Fay, FuKun W Hoffmann, Peter R Hoffmann

Abstract read
In one paragraph

Article in Journal of leukocyte biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.2field-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

30 citing papers in PubMed, 47 citations in OpenAlex.

  1. Review
  2. ProteinJournal of pharmaceutical analysis · 2026
    Review
  3. Review
  4. Review
  5. Selenoprotein K at the intersection of cellular pathways.Archives of biochemistry and biophysics · 2025
    Review
  6. Neutrophil elastase activates macrophage calpain as a mechanism for phagocytic failure.American journal of physiology. Lung cellular and molecular physiology · 2025
    Article
  7. Article
  8. Article
  9. Article
  10. Relationship between selenium status, selenoproteins and COVID-19 and other inflammatory diseases: A critical review.Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2023
    Review
  11. 1,25(OH)Nutrients · 2022
    Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. ProteinOpen biology · 2021
    Review
  19. Review
  20. Protein Palmitoylation in Leukocyte Signaling and Function.Frontiers in cell and developmental biology · 2020
    Review
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 2 institutions in 2 countries.

Robert L NortonDepartment of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA; and.
Gregory J FredericksDepartment of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA; and.
Zhi HuangDepartment of Biotechnology, College of Life Science and Technology, Jinan University, Guangzhou, P. R. China.
Jeffrey D FayDepartment of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA; and.
FuKun W HoffmannDepartment of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA; and.
Peter R HoffmannDepartment of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA; and peterrh@hawaii.edu.
University of Hawaiʻi at Mānoa · USJinan University · CN

Funding

WORLDWIDE EPIDEMIOLOGY &EPIZOOTIOLOGY OF HANTAVIRUSG12RR003061 · NCRR · UNIVERSITY OF HAWAII AT MANOA · PI ALLEN, JOHN A · 1986 to 2011
$32.3M
RESEARCH DESIGN, BIOSTATISTICS AND RESEARCH ETHICS COREG12MD007601 · NIMHD · UNIVERSITY OF HAWAII AT MANOA · PI BERRY, MARLA J · 2012 to 2016
$13.0M
Small Grants ProgramP30GM114737 · NIGMS · UNIVERSITY OF HAWAII AT MANOA · PI YANAGIHARA, RICHARD · 2015 to 2022
$8.1M
Pilot Project ProgramP30GM103341 · NIGMS · UNIVERSITY OF HAWAII AT MANOA · PI SHOHET, RALPH V. · 2012 to 2016
$5.5M
Selenoprotein K modulates calcium-dependent signaling in immune cellsR01AI089999 · NIAID · UNIVERSITY OF HAWAII AT MANOA · PI HOFFMANN, PETER R · 2010 to 2020
$3.6M
NCRR NIH HHS G12 RR003061NIAID NIH HHS R01 AI089999NIGMS NIH HHS P30 GM103341NIGMS NIH HHS P30 GM114737NIMHD NIH HHS G12 MD007601
6 · The paper itself

Abstract

Effective activation of macrophages through phagocytic Fcγ receptors (FcγR) has been shown to require selenoprotein K (Selk). We set out to determine whether the FcγR-mediated uptake process itself also requires Selk and potential underlying mechanisms. Macrophages from Selk knockout (KO) mice were less efficient compared with wild-type (WT) controls in engulfing IgG-coated fluorescent beads. Using LC-MS/MS to screen for Selk-binding partners involved in FcγR-mediated phagocytosis, we identified Arf-GAP with SH3 domain, ANK repeat, and PH domain-containing protein 2 (ASAP2). Coimmunoprecipitation assays confirmed interactions between Selk and ASAP2. Selk was required for ASAP2 to be cleaved by calpain-2 within the Bin/Amphiphysin/Rvs (BAR) domain of ASAP2. BAR domains promote membrane association, which was consistent with our data showing that Selk deficiency led to retention of ASAP2 within the phagocytic cup. Because Selk was recently identified as a cofactor for the palmitoylation of certain proteins, we investigated whether ASAP2 was palmitoylated and whether this was related to its cleavage by calpain-2. Acyl/biotin exchange assays and MALDI-TOF analysis showed that cysteine-86 in ASAP2 was palmitoylated in WT, but to a much lesser extent in KO, mouse macrophages. Inhibitors of either palmitoylation or calpain-2 cleavage and rescue experiments with different versions of Selk demonstrated that Selk-dependent palmitoylation of ASAP2 leads to cleavage by calpain-2 within the BAR domain, which releases this protein from the maturing phagocytic cup. Overall, these findings identify ASAP2 as a new target of Selk-dependent palmitoylation and reveal a new mechanism regulating the efficiency of FcγR-mediated phagocytosis.

Indexed as

LipoylationPhagocytosisADP-Ribosylation FactorsAnimalsCalpainGTPase-Activating ProteinsMacrophagesMiceMice, Inbred C57BLMice, KnockoutModels, BiologicalProtein BindingRAW 264.7 CellsReceptors, IgGSelenoproteinsADP-Ribosylation FactorsASAP2 protein, mouseCalpainGTPase-Activating ProteinsReceptors, IgGselenoprotein K, mouseSelenoproteinsimmune complexmacrophagepalmitatephagocytic cupselenium

Identifiers

PMID27601625
PMCPMC5235904
OpenAlexW2520404174

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.