Evidence map›Paper›PMID 23882690›Full record

ArticleInvestigative ophthalmology & visual science2013

Role of PKCα activation of Src, PI-3K/AKT, and ERK in EGF-stimulated proliferation of rat and human conjunctival goblet cells.

Dayu Li, Marie A Shatos, Robin R Hodges, Darlene A Dartt

Open access · bronzeAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

18 citing papers in PubMed, 35 citations in OpenAlex.

  1. PKCActa pharmaceutica Sinica. B · 2024
    Article
  2. Article
  3. Frontiers in cellular and infection microbiology · 2023
    Article
  4. Article
  5. Protein Kinase C-α Is a Gatekeeper ofInfection and immunity · 2022
    Article
  6. Impact of P2XInternational journal of molecular sciences · 2021
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Neither non-toxigenicBMJ open ophthalmology · 2017
    Article
  13. Review
  14. Article
  15. Molecular determinants of acute kidney injury.Journal of injury & violence research · 2015
    Review
  16. Review
  17. Silencing of Src by siRNA inhibits laryngeal carcinoma growth through the Src/PI-3 K/Akt pathway in vitro and in vivo.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014
    Article
  18. 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

4 authors at 2 institutions in 1 country.

Dayu LiSchepens Eye Research Institute/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
Marie A Shatos
Robin R Hodges
Darlene A Dartt
Massachusetts Eye and Ear Infirmary · USSmith-Kettlewell Eye Research Institute · US

Funding

Conjunctival Goblet Cell Mucin Secretion in Inflammation and Its ResolutionR01EY019470 · NEI · SCHEPENS EYE RESEARCH INSTITUTE · PI DARTT, DARLENE A · 2009 to 2023
$7.4M
NEI NIH HHS EY019470NEI NIH HHS R01 EY019470
6 · The paper itself

Abstract

purposeTo determine the order and components of the signaling pathway utilized by epidermal growth factor (EGF) to stimulate conjunctival goblet cell proliferation.

methodsGoblet cells from rat bulbar and forniceal conjunctiva and human bulbar conjunctiva were grown in organ culture. Goblet cells (GCs) were serum starved for 24 hours and preincubated with inhibitors for 30 minutes or small interfering RNA (siRNA) for 48 hours prior to addition of EGF. Proliferation was then measured or Western blot analysis was performed using antibodies against phosphorylated protein kinase B (AKT), extracellular signal-regulated kinase 1/2 (ERK1/2), or the non-receptor tyrosine kinase Src. Rat GCs were also incubated with adenoviruses expressing dominant negative protein kinase Cα (DNPKCα) or constitutively activated protein kinase Cα (myrPKCα), and activation of AKT and ERK1/2 was determined by Western blot analysis.

resultsInhibitors of phosphoinositol-3 kinase (PI-3K)/AKT pathway blocked EGF-stimulated ERK1/2 activation and GC proliferation. Inhibitors of EGF-stimulated ERK1/2 activity did not inhibit AKT activation but blocked proliferation. DNPKCα blocked EGF-stimulated activation of AKT and ERK1/2 while myrPKCα increased activation of these kinases. Inhibitors of PI-3K, ERK1/2, and protein kinase C (PKC) blocked myrPKCα-stimulated GC proliferation. EGF and myrPKCα increased phosphorylation of Src, and inhibition of Src with the chemical inhibitor PP1 or siRNA inhibited EGF-stimulated GC proliferation.

conclusionsWe found that EGF activates a major pathway to stimulate goblet cell proliferation. This pathway consists of induction of phospholipase C (PLC)γ to activate PKCα. Active PKCα phosphorylates Src to induce PI-3K to phosphorylate AKT that subsequently activates the ERK1/2 cascade to stimulate goblet cell proliferation.

Indexed as

AnimalsCell ProliferationChromonesConjunctivaEnzyme InhibitorsEpidermal Growth FactorGoblet CellsHumansMaleMAP Kinase Signaling SystemMitogen-Activated Protein Kinase 1MorpholinesOrgan Culture TechniquesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylation2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-oneAKT1 protein, humanAkt1 protein, ratChromonesEnzyme InhibitorsEpidermal Growth FactorMAPK1 protein, humanMitogen-Activated Protein Kinase 1MorpholinesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein Kinase C-alphaProto-Oncogene Proteins c-aktProto-Oncogene Proteins pp60(c-src)RNA, Small Interferingcell proliferationconjunctivaEGFgoblet cells

Identifiers

PMID23882690
PMCPMC3756614
OpenAlexW2025562733

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.