Evidence map›Paper›PMID 30261270›Full record

ArticleCellular signalling2019

PKCδ stimulates macropinocytosis via activation of SSH1-cofilin pathway.

Bhupesh Singla, Hui-Ping Lin, Pushpankur Ghoshal, Mary Cherian-Shaw, Gábor Csányi

Abstract read
In one paragraph

Article in Cellular signalling, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.2field-weighted citation impact, top 24% 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

20 citing papers in PubMed, 24 citations in OpenAlex.

  1. Myeloid Cell-Specific Deletion of LGR4 Suppresses Atherosclerotic Lesion Formation.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Article
  2. Article
  3. Article
  4. Review
  5. EGF-Induced Macropinocytosis Promotes NAV1-Dependent Internalization of Occludin in Keratinocytes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  6. Article
  7. Membrane Ruffles: Composition, Function, Formation and Visualization.International journal of molecular sciences · 2024
    Review
  8. Article
  9. Matricellular proteins in atherosclerosis development.Matrix biology : journal of the International Society for Matrix Biology · 2023
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Cofilin Signaling in the CNS Physiology and Neurodegeneration.International journal of molecular sciences · 2021
    Review
  15. Article
  16. Article
  17. Article
  18. Interleukin 10 promotes macrophage uptake of HDL and LDL by stimulating fluid-phase endocytosis.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020
    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

5 authors at 1 institution in 1 country.

Bhupesh SinglaVascular Biology Center, 1460 Laney Walker Blvd., Augusta University, Medical College of Georgia, Augusta, GA 30912, USA.
Hui-Ping LinVascular Biology Center, 1460 Laney Walker Blvd., Augusta University, Medical College of Georgia, Augusta, GA 30912, USA.
Pushpankur GhoshalVascular Biology Center, 1460 Laney Walker Blvd., Augusta University, Medical College of Georgia, Augusta, GA 30912, USA.
Mary Cherian-ShawVascular Biology Center, 1460 Laney Walker Blvd., Augusta University, Medical College of Georgia, Augusta, GA 30912, USA.
Gábor CsányiVascular Biology Center, 1460 Laney Walker Blvd., Augusta University, Medical College of Georgia, Augusta, GA 30912, USA; Department of Pharmacology and Toxicology, 1460 Laney Walker Blvd., Augusta University, Medical College of Georgia, Augusta, GA 30912, USA. Electronic address: gcsanyi@augusta.edu.
Augusta University · US

Funding

Lipid macropinocytosis: a novel target in atherosclerotic cardiovascular diseaseR01HL139562 · NHLBI · AUGUSTA UNIVERSITY · PI CSANYI, GABOR · 2018 to 2022
$1.9M
A Novel Role of Macrophage TSP1-CD47 Signaling in AtherosclerosisR00HL114648 · NHLBI · AUGUSTA UNIVERSITY · PI CSANYI, GABOR · 2015 to 2017
$747k
A Novel Role of Macrophage TSP1-CD47 Signaling in AtherosclerosisK99HL114648 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CSANYI, GABOR · 2013 to 2014
$178k
NHLBI NIH HHS K99 HL114648NHLBI NIH HHS R00 HL114648NHLBI NIH HHS R01 HL139562
6 · The paper itself

Abstract

Macropinocytosis is an actin-dependent endocytic mechanism mediating internalization of extracellular fluid and associated solutes into cells. The present study was designed to identify the specific protein kinase C (PKC) isoform(s) and downstream effectors regulating actin dynamics during macropinocytosis. We utilized various cellular and molecular biology techniques, pharmacological inhibitors and genetically modified mice to study the signaling mechanisms mediating macropinocytosis in macrophages. The qRT-PCR experiments identified PKCδ as the predominant PKC isoform in macrophages. Scanning electron microscopy and flow cytometry analysis of FITC-dextran internalization demonstrated the functional role of PKCδ in phorbol ester- and hepatocyte growth factor (HGF)-induced macropinocytosis. Western blot analysis demonstrated that phorbol ester and HGF stimulate activation of slingshot phosphatase homolog 1 (SSH1) and induce cofilin Ser-3 dephosphorylation via PKCδ in macrophages. Silencing of SSH1 inhibited cofilin dephosphorylation and macropinocytosis stimulation. Interestingly, we also found that incubation of macrophages with BMS-5, a potent inhibitor of LIM kinase, does not stimulate macropinocytosis. In conclusion, the findings of the present study demonstrate a previously unidentified mechanism by which PKCδ via activation of SSH1 and cofilin dephosphorylation stimulates membrane ruffle formation and macropinocytosis. The results of the present study may contribute to a better understanding of the regulatory mechanisms during macrophage macropinocytosis.

Indexed as

PinocytosisSignal TransductionActin Depolymerizing FactorsAnimalsLim KinasesMacrophagesMaleMicePhosphoprotein PhosphatasesPhosphorylationProtein Kinase C-deltaRAW 264.7 CellsActin Depolymerizing FactorsLimk1 protein, mouseLim KinasesPhosphoprotein PhosphatasesPrkcd protein, mouseProtein Kinase C-deltaSSH1 protein, mouseActin remodelingCofilinMacrophagesMacropinocytosisProtein kinase CSSH1

Identifiers

PMID30261270
PMCPMC6289628
OpenAlexW2893769676

What OpenQuestion holds

Textmetadata
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.