Evidence map›Paper›PMID 25232008›Full record

ArticleMolecular biology of the cell2014

A1 adenosine receptor-stimulated exocytosis in bladder umbrella cells requires phosphorylation of ADAM17 Ser-811 and EGF receptor transactivation.

H Sandeep Prakasam, Luciana I Gallo, Hui Li, Wily G Ruiz, Kenneth R Hallows, Gerard Apodaca

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 28% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Contribution of ADAM17 and related ADAMs in cardiovascular diseases.Cellular and molecular life sciences : CMLS · 2021
    Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. RAB27B requirement for stretch-induced exocytosis in bladder umbrella cells.American journal of physiology. Cell physiology · 2018
    Article
  11. 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

6 authors at 1 institution in 1 country.

H Sandeep PrakasamDepartments of Medicine and Cell Biology, University of Pittsburgh, Pittsburgh, PA 15261.
Luciana I GalloDepartments of Medicine and Cell Biology, University of Pittsburgh, Pittsburgh, PA 15261.
Hui LiDepartments of Medicine and Cell Biology, University of Pittsburgh, Pittsburgh, PA 15261.
Wily G RuizDepartments of Medicine and Cell Biology, University of Pittsburgh, Pittsburgh, PA 15261.
Kenneth R HallowsDepartments of Medicine and Cell Biology, University of Pittsburgh, Pittsburgh, PA 15261.
Gerard ApodacaDepartments of Medicine and Cell Biology, University of Pittsburgh, Pittsburgh, PA 15261 gla6@pitt.edu.
University of Pittsburgh · US

Funding

Single Nephron and MetabolomicsP30DK079307 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R · 2008 to 2022
$13.4M
Endocytic and Exocytic Traffic in Bladder UroepitheliumR37DK054425 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI APODACA, GERARD L · 2004 to 2013
$3.2M
Mechanisms and Relevance of Sodium Transport Regulation by AMPKR01DK075048 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HALLOWS, KENNETH R · 2007 to 2015
$2.5M
Adenosine Receptor Function in Bladder UroepitheliumR01DK077777 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI APODACA, GERARD L · 2008 to 2012
$2.1M
NIDDK NIH HHS P30 DK079307NIDDK NIH HHS P30-DK079307NIDDK NIH HHS R01 DK075048NIDDK NIH HHS R01-DK075048NIDDK NIH HHS R01 DK077777NIDDK NIH HHS R01-DK077777NIDDK NIH HHS R37 DK054425NIDDK NIH HHS R37-DK54425
6 · The paper itself

Abstract

Despite the importance of ADAM17-dependent cleavage in normal biology and disease, the physiological cues that trigger its activity, the effector pathways that promote its function, and the mechanisms that control its activity, particularly the role of phosphorylation, remain unresolved. Using native bladder epithelium, in some cases transduced with adenoviruses encoding small interfering RNA, we observe that stimulation of apically localized A1 adenosine receptors (A1ARs) triggers a Gi-Gβγ-phospholipase C-protein kinase C (PKC) cascade that promotes ADAM17-dependent HB-EGF cleavage, EGFR transactivation, and apical exocytosis. We further show that the cytoplasmic tail of rat ADAM17 contains a conserved serine residue at position 811, which resides in a canonical PKC phosphorylation site, and is phosphorylated in response to A1AR activation. Preventing this phosphorylation event by expression of a nonphosphorylatable ADAM17(S811A) mutant or expression of a tail-minus construct inhibits A1AR-stimulated, ADAM17-dependent HB-EGF cleavage. Furthermore, expression of ADAM17(S811A) in bladder tissues impairs A1AR-induced apical exocytosis. We conclude that adenosine-stimulated exocytosis requires PKC- and ADAM17-dependent EGFR transactivation and that the function of ADAM17 in this pathway depends on the phosphorylation state of Ser-811 in its cytoplasmic domain.

Indexed as

ADAM17 ProteinADAM ProteinsAnimalsEpithelial CellsErbB ReceptorsExocytosisHumansPhosphorylationRatsReceptor, Adenosine A1Transcriptional ActivationUrinary BladderADAM17 ProteinADAM17 protein, humanAdam17 protein, ratADAM ProteinsErbB ReceptorsReceptor, Adenosine A1

Identifiers

PMID25232008
PMCPMC4230785
OpenAlexW2024938296

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.