Evidence map›Paper›PMID 23211419›Full record

ArticleMolecular & cellular proteomics : MCP2013

Identification and selected reaction monitoring (SRM) quantification of endocytosis factors associated with Numb.

Jonathan R Krieger, Paul Taylor, Aaron S Gajadhar, Abhijit Guha, Michael F Moran, C Jane McGlade

Open access · hybridAbstract read
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.0field-weighted citation impact, top 15% 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

33 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. SGC-AAK1-1: A Chemical Probe Targeting AAK1 and BMP2K.ACS medicinal chemistry letters · 2020
    Article
  14. Article
  15. Exon 3 of theG3 (Bethesda, Md.) · 2019
    Article
  16. Serine/Threonine Protein Kinase STK16.International journal of molecular sciences · 2019
    Review
  17. Review
  18. Article
  19. Article
  20. 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 3 institutions in 1 country.

Jonathan R KriegerDepartment of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 2M9, Canada.
Paul Taylor
Aaron S Gajadhar
Abhijit Guha
Michael F Moran
C Jane McGlade
Hospital for Sick Children · CASickKids Foundation · CAUniversity of Toronto · CA

Funding

Canadian Institutes of Health Research MOP-102536Canadian Institutes of Health Research MOP-106507
6 · The paper itself

Abstract

Numb is an endocytic adaptor protein that regulates the endocytosis and trafficking of transmembrane receptors including Notch, E-cadherin, and integrins. Vertebrate Numb is alternatively spliced at exons 3 and 9 to give rise to four protein isoforms. Expression of these isoforms varies at different developmental stages, and although the function of Numb isoforms containing exon 3 has been studied, the role of exon 9 inclusion has not been shown. Here we use affinity purification and tandem mass spectrometry to identify Numb associated proteins, including novel interactions with REPS1, BMP2K, and BCR. In vitro binding measurements indicated exon 9-independent Numb interaction with REPS1 and Eps15 EH domains. Selected reaction monitoring mass spectrometry was used to quantitatively compare the proteins associated with the p72 and p66 Numb isoforms, which differ by the exon 9 region. This showed that significantly more EPS15 and three AP-2 subunit proteins bound Numb isoforms containing exon 9. The EPS15 preference for exon 9-containing Numb was confirmed in intact cells by using a proximity ligation assay. Finally, we used multiplexed selected reaction monitoring mass spectrometry to assess the dynamic regulation of Numb association with endocytic proteins. Numb hyper-phosphorylation resulted in disassociation of Numb endocytic complexes, while inhibition of endocytosis did not alter Numb association with the AP-2 complex but altered recruitment of EPS15, REPS1, and BMP2K. Hence, quantitative mass spectrometric analysis of Numb protein-protein interactions has provided new insights into the assembly and regulation of protein complexes important in development and cancer.

Indexed as

Adaptor Proteins, Signal TransducingAmino Acid SequenceAnimalsBinding SitesCalcium-Binding ProteinsCarrier ProteinsChromatography, LiquidEndocytosisExonsGene Expression RegulationHEK293 CellsHumansKruppel-Like Transcription FactorsMembrane ProteinsMiceMolecular Sequence DataAdaptor Proteins, Signal TransducingBCR protein, humanCalcium-Binding ProteinsCarrier ProteinsEPS15 protein, humanKLF12 protein, humanKruppel-Like Transcription FactorsMembrane ProteinsNerve Tissue ProteinsNumb protein, mouseProtein IsoformsProto-Oncogene Proteins c-bcrREPS1 protein, human

Identifiers

PMID23211419
PMCPMC3567869
OpenAlexW2114241266

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.