Evidence map›Paper›PMID 18276747›Full record

ArticleEndocrinology2008

Endothelin-converting enzyme-1 degrades internalized somatostatin-14.

Dirk Roosterman, Cordula Kempkes, Graeme S Cottrell, Benjamin E Padilla, Nigel W Bunnett, Christoph W Turck, Martin Steinhoff

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Endocrinology, 2008. 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
4.6field-weighted citation impact, top 5% 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, 38 citations in OpenAlex.

  1. Article
  2. Combination treatments to enhance peptide receptor radionuclide therapy of neuroendocrine tumours.European journal of nuclear medicine and molecular imaging · 2020
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Roles of proteolysis in regulation of GPCR function.British journal of pharmacology · 2013
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Protein phosphatase 2A mediates resensitization of the neurokinin 1 receptor.American journal of physiology. Cell physiology · 2011
    Article
  14. Article
  15. Endosomes: a legitimate platform for the signaling train.Proceedings of the National Academy of Sciences of the United States of America · 2009
    Review
  16. Article
  17. 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

7 authors at 2 institutions in 2 countries.

Dirk RoostermanDepartment of Dermatology, Interdisziplinäres Zentrum für Klinische Forschung Münster, and Ludwig Bolzmann Institute for Cell and Immunobiology of the Skin, University Münster, D-48149 Münster, Germany. roosterman@gmx.net
Cordula Kempkes
Graeme S Cottrell
Benjamin E Padilla
Nigel W Bunnett
Christoph W Turck
Martin Steinhoff
University of California, San Francisco · USMax Planck Society · DE

Funding

REGULATION OF CELLULAR RESPONSES TO NEUROPEPTIDESR37DK039957 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BUNNETT, NIGEL W · 2000 to 2010
$3.2M
REGULATION OF SIGNALING BY CELL SURFACE PROTEOLYSISR01DK043207 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BUNNETT, NIGEL W · 1993 to 2011
$1.7M
REGULATION OF SIGNALING BY CELL-SURFACE PROTEOLYSISR56DK043207 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BUNNETT, NIGEL W · 2010 to 2010
$348k
REGULATION OF CELLULAR RESPONSES TO NEUROPEPTIDESR01DK039957 · NIDDK · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI BUNNETT, NIGEL W · 1987 to 1998
–
NIDDK NIH HHS DK39957NIDDK NIH HHS DK43207NIDDK NIH HHS R01 DK039957NIDDK NIH HHS R01 DK043207NIDDK NIH HHS R37 DK039957NIDDK NIH HHS R56 DK043207
6 · The paper itself

Abstract

Agonist-induced internalization of somatostatin receptors (ssts) determines subsequent cellular responsiveness to peptide agonists and influences sst receptor scintigraphy. To investigate sst2A trafficking, rat sst2A tagged with epitope was expressed in human embryonic kidney cells and tracked by antibody labeling. Confocal microscopical analysis revealed that stimulation with sst and octreotide induced internalization of sst2A. Internalized sst2A remained sequestrated within early endosomes, and 60 min after stimulation, internalized sst2A still colocalized with beta-arrestin1-enhanced green fluorescence protein (EGFP), endothelin-converting enzyme-1 (ECE-1), and rab5a. Internalized (125)I-Tyr(11)-SST-14 was rapidly hydrolyzed by endosomal endopeptidases, with radioactive metabolites being released from the cell. Internalized (125)I-Tyr(1)-octreotide accumulated as an intact peptide and was released from the cell as an intact peptide ligand. We have identified ECE-1 as one of the endopeptidases responsible for inactivation of internalized SST-14. ECE-1-mediated cleavage of SST-14 was inhibited by the specific ECE-1 inhibitor, SM-19712, and by preventing acidification of endosomes using bafilomycin A(1). ECE-1 cleaved SST-14 but not octreotide in an acidic environment. The metallopeptidases angiotensin-1 converting enzyme and ECE-2 did not hydrolyze SST-14 or octreotide. Our results show for the first time that stimulation with SST-14 and octreotide induced sequestration of sst2A into early endosomes and that endocytosed SST-14 is degraded by endopeptidases located in early endosomes. Furthermore, octreotide was not degraded by endosomal peptidases and was released as an intact peptide. This mechanism may explain functional differences between octreotide and SST-14 after sst2A stimulation. Moreover, further investigation of endopeptidase-regulated trafficking of neuropeptides may result in novel concepts of neuropeptide receptor inactivation in cancer diagnosis.

Indexed as

EndocytosisProtein Processing, Post-TranslationalAmino Acid SequenceArrestinsAspartic Acid Endopeptidasesbeta-ArrestinsBinding SitesCells, CulturedEndopeptidasesEndosomesEndothelin-Converting EnzymesHumansIodine RadioisotopesMetalloendopeptidasesOctreotideProtein BindingArrestinsAspartic Acid Endopeptidasesbeta-ArrestinsECE1 protein, humanECE2 protein, humanEndopeptidasesEndothelin-Converting EnzymesIodine RadioisotopesMetalloendopeptidasesOctreotideReceptors, SomatostatinSomatostatinsomatostatin receptor sst2A

Identifiers

PMID18276747
PMCPMC2329273
OpenAlexW2135037322

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.