Evidence map›Paper›PMID 20817724›Full record

ArticleThe Journal of biological chemistry2010

Secretion stimulates intramembrane proteolysis of a secretory granule membrane enzyme.

Chitra Rajagopal, Kathryn L Stone, Richard E Mains, Betty A Eipper

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Article
  3. Physiological signaling in the absence of amidated peptides.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. The many substrates of presenilin/γ-secretase.Journal of Alzheimer's disease : JAD · 2011
    Review
  14. Article
  15. Signaling from the secretory granule to the nucleus.Critical reviews in biochemistry and molecular biology
    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

4 authors at 2 institutions in 1 country.

Chitra RajagopalDepartments of Molecular, Microbial, and Structural Biology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
Kathryn L Stone
Richard E Mains
Betty A Eipper
UConn Health · USW. M. Keck Foundation · US

Funding

YALE UNIVERSITY CLINICAL AND TRANSLATIONAL SCIENCE AWARD PROGRAMUL1RR024139 · NCRR · YALE UNIVERSITY · PI SHERWIN, ROBERT S · 2006 to 2011
$56.8M
Yale/NIDA Neuroproteomics Research CenterP30DA018343 · NIDA · YALE UNIVERSITY · PI Marina R Picciotto · 2004 to 2026
$37.1M
BIOCHEMISTRY AND PHYSIOLOGY OF PEPTIDE AMIDATIONR01DK032949 · NIDDK · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI EIPPER, ELIZABETH ANNE, KING, STEPHEN M · 1986 to 2017
$6.4M
BIOCHEMISTRY AND PHYSIOLOGY OF PEPTIDE AMIDATIONR37DK032949 · NIDDK · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI EIPPER, ELIZABETH A · 1989 to 2004
$2.8M
LTQ-Orbitrap Mass Spectrometer for Yale University Keck LaboratoryS10RR024617 · NCRR · YALE UNIVERSITY · PI GULCICEK, EROL E · 2008 to 2008
$500k
BIOCHEMISTRY AND PHYSIOLOGY OF PEPTIDE AMIDATIONR56DK032949 · NIDDK · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI EIPPER, ELIZABETH A · 2005 to 2005
$104k
NCRR NIH HHS 1S10RR024617NCRR NIH HHS S10 RR024617NCRR NIH HHS UL1 RR024139NCRR NIH HHS UL1RR024139NIDA NIH HHS P30 DA018343NIDDK NIH HHS DK32949NIDDK NIH HHS R01 DK032949NIDDK NIH HHS R37 DK032949NIDDK NIH HHS R56 DK032949
6 · The paper itself

Abstract

Regulated intramembrane proteolysis, a highly conserved process employed by diverse regulatory pathways, can release soluble fragments that directly or indirectly modulate gene expression. In this study we used pharmacological tools to identify peptidylglycine α-amidating monooxygenase (PAM), a type I secretory granule membrane protein, as a γ-secretase substrate. PAM, an essential enzyme, catalyzes the final step in the synthesis of the majority of neuropeptides that control metabolic homeostasis. Mass spectroscopy was most consistent with the presence of multiple closely spaced NH(2) termini, suggesting that cleavage occurred near the middle of the PAM transmembrane domain. The luminal domains of PAM must undergo a series of prohormone convertase or α-secretase-mediated cleavages before the remaining transmembrane domain/cytosolic domain fragment can undergo a γ-secretase-like cleavage. Cleavage by γ-secretase generates a soluble fragment of the cytosolic domain (sf-CD) that is known to localize to the nucleus. Although PAM sf-CD is unstable in AtT-20 corticotroph tumor cells, it is readily detected in primary rat anterior pituitary cells. PAM isoform expression, which is tissue-specific and developmentally regulated, affects the efficiency with which sf-CD is produced. sf-CD levels are also modulated by the phosphorylation status of the cytosolic domain and by the ability of the cytosolic domain to interact with cytosolic proteins. sf-CD is produced by primary rat anterior pituitary cells in response to secretogogue, suggesting that sf-CD acts as a signaling molecule relaying information about secretion from the secretory granule to the nucleus.

Indexed as

Amyloid Precursor Protein SecretasesAnimalsCell Line, TumorCell NucleusFemaleIsoenzymesMaleMixed Function OxygenasesMultienzyme ComplexesNeuropeptidesPituitary Gland, AnteriorProtein Structure, TertiaryRatsSecretory VesiclesSignal TransductionAmyloid Precursor Protein SecretasesIsoenzymesMixed Function OxygenasesMultienzyme ComplexesNeuropeptidespeptidylglycine monooxygenase

Identifiers

PMID20817724
PMCPMC2966079
OpenAlexW1979168227

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.