Evidence map›Paper›PMID 12606711›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2003

Integrin beta cytoplasmic domain interactions with phosphotyrosine-binding domains: a structural prototype for diversity in integrin signaling.

David A Calderwood, Yosuke Fujioka, Jose M de Pereda, Begoña García-Alvarez, Tetsuya Nakamoto, Ben Margolis, C Jane McGlade, Robert C Liddington, Mark H Ginsberg

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers.

0numbers the graph read from it
0cells of the map it votes in
179citing papers in PubMed
8.1field-weighted citation impact, top 1% 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

179 citing papers in PubMed, 423 citations in OpenAlex.

  1. Article
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  8. Spatial N-glycan rearrangement on αNature communications · 2025
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  9. Review
  10. Review
  11. Kindlin Regulates Mechanosensitive Activation and Adhesion Assembly of Integrin beta6.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  12. Article
  13. Article
  14. Integrating integrins with the hallmarks of cancer.Matrix biology : journal of the International Society for Matrix Biology · 2024
    Review
  15. Article
  16. Identification of Tensin-3 as a MALT1 substrate that controls B cell adhesion and lymphoma dissemination.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  17. Article
  18. The role of tensins in malignant neoplasms.Archives of medical science : AMS · 2023
    Article
  19. Article
  20. Review

119 more citing papers are in PubMed but not listed here.

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

9 authors at 5 institutions in 2 countries.

David A CalderwoodDivision of Vascular Biology, Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Yosuke Fujioka
Jose M de Pereda
Begoña García-Alvarez
Tetsuya Nakamoto
Ben Margolis
C Jane McGlade
Robert C Liddington
Mark H Ginsberg
University of Michigan–Ann Arbor · USSanford Burnham Prebys Medical Discovery Institute · USScripps Research Institute · USHospital for Sick Children · CAHoward Hughes Medical Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The cytoplasmic domains (tails) of heterodimeric integrin adhesion receptors mediate integrins' biological functions by binding to cytoplasmic proteins. Most integrin beta tails contain one or two NPXYF motifs that can form beta turns. These motifs are part of a canonical recognition sequence for phosphotyrosine-binding (PTB) domains, protein modules that are present in a wide variety of signaling and cytoskeletal proteins. Indeed, talin and ICAP1-alpha bind to integrin beta tails by means of a PTB domain-NPXY ligand interaction. To assess the generality of this interaction we examined the binding of a series of recombinant PTB domains to a panel of short integrin beta tails. In addition to the known integrin-binding proteins, we found that Numb (a negative regulator of Notch signaling) and Dok-1 (a signaling adaptor involved in cell migration) and their isolated PTB domain bound to integrin tails. Furthermore, Dok-1 physically associated with integrin alpha IIb beta 3. Mutations of the integrin beta tails confirmed that these interactions are canonical PTB domain-ligand interactions. First, the interactions were blocked by mutation of an NPXY motif in the integrin tail. Second, integrin class-specific interactions were observed with the PTB domains of Dab, EPS8, and tensin. We used this specificity, and a molecular model of an integrin beta tail-PTB domain interaction to predict critical interacting residues. The importance of these residues was confirmed by generation of gain- and loss-of-function mutations in beta 7 and beta 3 tails. These data establish that short integrin beta tails interact with a large number of PTB domain-containing proteins through a structurally conserved mechanism.

Indexed as

AlanineAmino Acid SequenceAnimalsCHO CellsCricetinaeCytoplasmDatabases as TopicDNADose-Response Relationship, DrugElectrophoresis, Polyacrylamide GelGlutathione TransferaseHumansIntegrin beta ChainsIntegrinsMiceModels, MolecularAlanineDNAGlutathione TransferaseIntegrin beta ChainsIntegrinsPhosphotyrosineRecombinant Fusion ProteinsRecombinant ProteinsTyrosine

Identifiers

PMID12606711
PMCPMC151330
OpenAlexW1990883677

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.