Evidence map›Paper›PMID 11483505›Full record

ArticleThe EMBO journal2001

Dephosphorylation of beta2-syntrophin and Ca2+/mu-calpain-mediated cleavage of ICA512 upon stimulation of insulin secretion.

T Ort, S Voronov, J Guo, K Zawalich, S C Froehner, W Zawalich, M Solimena

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

39 citing papers in PubMed, 106 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Calpain-generated natural protein fragments as short-lived substrates of the N-end rule pathway.Proceedings of the National Academy of Sciences of the United States of America · 2014
    Article
  18. Article
  19. Review
  20. Syntrophin proteins as Santa Claus: role(s) in cell signal transduction.Cellular and molecular life sciences : CMLS · 2013
    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

7 authors at 1 institution in 1 country.

T OrtDepartment of Internal Medicine, Section of Endocrinology, School of Nursing, Yale University School of Medicine, New Haven, CT 06520-8020, USA.
S Voronov
J Guo
K Zawalich
S C Froehner
W Zawalich
M Solimena
Yale University · US

Funding

Yale Diabetes Research CenterP30DK045735 · NIDDK · YALE UNIVERSITY · PI Richard A Flavell · 1993 to 2026
$44.0M
ROLE OF MHC CLASS 2 MOLECULES ON THE DEVELOPMENT OF T CELL TOLERANCEP01DK053015 · NIDDK · YALE UNIVERSITY · PI JANEWAY, CHARLES A · 1997 to 2002
$3.2M
PHOSPHOINOSITIDE HYDROLYSIS &BETA CELL SECRETIONR01DK041230 · NIDDK · YALE UNIVERSITY · PI ZAWALICH, WALTER S. · 1989 to 2006
$2.3M
MOLECULAR AND FUNCTIONAL ANALYSIS OF ICA 512R01DK054913 · NIDDK · YALE UNIVERSITY · PI DE CAMILLI, PIETRO V · 1998 to 2002
$491k
NIDDK NIH HHS DK41230NIDDK NIH HHS DK 45735NIDDK NIH HHS DK 53015NIDDK NIH HHS DK 54913NIDDK NIH HHS P30 DK045735NIDDK NIH HHS R01 DK041230
6 · The paper itself

Abstract

Islet cell autoantigen (ICA) 512 is a receptor-tyrosine phosphatase-like protein associated with the secretory granules of neuroendocrine cells, including pancreatic beta-cells. Binding of its cytoplasmic tail to beta2-syntrophin suggests that ICA512 connects secretory granules to the utrophin complex and the actin cytoskeleton. Here we show that stimulation of insulin secretion from INS-1 cells triggers the biosynthesis of pro-ICA512 and the degradation of its mature form. Inhibition of calpain, which is activated upon stimulation of insulin secretion, prevents the Ca2+-dependent proteolysis of ICA512. In vitro mu-calpain cleaves ICA512 between a putative PEST domain and the beta2-syntrophin binding site, whereas binding of ICA512 to beta2-syntrophin protects the former from cleavage. beta2-syntrophin and its F-actin-binding protein utrophin are enriched in subcellular fractions containing secretory granules. ICA512 preferentially binds phospho-beta2-syntrophin and stimulation of insulin secretion induces the Ca2+-dependent, okadaic acid-sensitive dephosphorylation of beta2-syntrophin. Similarly to calpeptin, okadaic acid inhibits ICA512 proteolysis and insulin secretion. Thus, stimulation of insulin secretion might promote the mobilization of secretory granules by inducing the dissociation of ICA512 from beta2-syntrophin-utrophin complexes and the cleavage of the ICA512 cytoplasmic tail by mu-calpain.

Indexed as

Amino Acid SequenceAnimalsAutoantigensCalpainCysteine Proteinase InhibitorsCytoskeletal ProteinsDipeptidesDystrophin-Associated ProteinsEnzyme ActivationEnzyme InhibitorsHumansInsulinInsulin SecretionIslets of LangerhansMembrane ProteinsMolecular Sequence DataAutoantigensCalpaincalpeptinCysteine Proteinase InhibitorsCytoskeletal ProteinsDipeptidesDystrophin-Associated ProteinsEnzyme InhibitorsInsulinMembrane ProteinsOkadaic AcidProtein PrecursorsProtein Tyrosine PhosphatasesPTPRN protein, humanPtprn protein, ratReceptor-Like Protein Tyrosine Phosphatases, Class 2Receptor-Like Protein Tyrosine Phosphatases, Class 8syntrophinUtrophin

Identifiers

PMID11483505
PMCPMC149140
OpenAlexW2157032387

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.