Evidence map›Paper›PMID 10644995›Full record

ArticleOncogene2000

Replacing two conserved tyrosines of the EphB2 receptor with glutamic acid prevents binding of SH2 domains without abrogating kinase activity and biological responses.

A H Zisch, C Pazzagli, A L Freeman, M Schneller, M Hadman, J W Smith, E Ruoslahti, E B Pasquale

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

52 citing papers in PubMed, 123 citations in OpenAlex.

  1. Article
  2. Article
  3. The Roles of EphB2 in Cancer.Frontiers in cell and developmental biology · 2022
    Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. EphB4: A promising target for upper aerodigestive malignancies.Biochimica et biophysica acta. Reviews on cancer · 2018
    Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Eph receptor signaling and ephrins.Cold Spring Harbor perspectives in biology · 2013
    Review
  20. 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

8 authors at 2 institutions in 2 countries.

A H ZischThe Burnham Institute, 10901 N. Torrey Pines Road, La Jolla, California, CA 92037, USA.
C Pazzagli
A L Freeman
M Schneller
M Hadman
J W Smith
E Ruoslahti
E B Pasquale
Sanford Burnham Prebys Medical Discovery Institute · USAugusta University · US

Funding

Tissue CultureP01HD025938 · NICHD · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI YAMAGUCHI, YU · 1989 to 2011
$13.6M
DEVELOPMENTAL BIOLOGY OF EPH-RELATED TYROSINE KINASESR01HD026351 · NICHD · BURNHAM INSTITUTE FOR MEDICAL RESEARCH · PI PASQUALE, ELENA B · 1995 to 1999
–
DEVELOPMENTAL BIOLOGY OF PROTEIN TYROSINE KINASESR29HD026351 · NICHD · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI PASQUALE, ELENA B · 1990 to 1994
–
NICHD NIH HHS HD25938NICHD NIH HHS HD26351
6 · The paper itself

Abstract

Eph receptor tyrosine kinases play key roles in pattern formation during embryonic development, but little is known about the mechanisms by which they elicit specific biological responses in cells. Here, we investigate the role of tyrosines 605 and 611 in the juxtamembrane region of EphB2, because they are conserved Eph receptor autophosphorylation sites and demonstrated binding sites for the SH2 domains of multiple signaling proteins. Mutation of tyrosines 605 and 611 to phenylalanine impaired EphB2 kinase activity, complicating analysis of their function as SH2 domain binding sites and their contribution to EphB2-mediated signaling. In contrast, mutation to the negatively charged glutamic acid disrupted SH2 domain binding without reducing EphB2 kinase activity. By using a panel of EphB2 mutants, we found that kinase activity is required for the changes in cell-matrix and cell - cell adhesion, cytoskeletal organization, and activation of mitogen-activated protein (MAP) kinases elicited by EphB2 in transiently transfected cells. Instead, the two juxtamembrane SH2 domain binding sites were dispensable for these effects. These results suggest that phosphorylation of tyrosines 605 and 611 is critical for EphB2-mediated cellular responses because it regulates EphB2 kinase activity.

Indexed as

Amino Acid SubstitutionConserved Sequencesrc Homology Domains3T3 CellsActinsAnimalsCell SizeCOS CellsEnzyme ActivationGlutamic AcidHumansMiceMice, KnockoutMitogen-Activated Protein KinasesMutagenesisPhenylalanineActinsGlutamic AcidMitogen-Activated Protein KinasesPhenylalanineReceptor, EphB2Receptor Protein-Tyrosine Kinasessrc-Family KinasesTyrosine

Identifiers

PMID10644995
OpenAlexW2084925637

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.