Evidence map›Paper›PMID 9736615›Full record

ArticleThe EMBO journal1998

Identification and analysis of PH domain-containing targets of phosphatidylinositol 3-kinase using a novel in vivo assay in yeast.

S J Isakoff, T Cardozo, J Andreev, Z Li, K M Ferguson, R Abagyan, M A Lemmon, A Aronheim, E Y Skolnik

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers.

0numbers the graph read from it
0cells of the map it votes in
123citing papers in PubMed
9.3field-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

123 citing papers in PubMed, 328 citations in OpenAlex.

  1. Article
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  4. Article
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  7. Article
  8. Article
  9. Dissecting peripheral protein-membrane interfaces.PLoS computational biology · 2022
    Article
  10. Review
  11. Review
  12. Class I PI3K Biology.Current topics in microbiology and immunology · 2022
    Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. PI3K isoforms in cell signalling and vesicle trafficking.Nature reviews. Molecular cell biology · 2019
    Review
  20. Article

63 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 3 institutions in 2 countries.

S J IsakoffThe Skirball Institute for Biomolecular Medicine and Department of Pharmacology, New York University Medical Center, New York, NY 10016, USA.
T Cardozo
J Andreev
Z Li
K M Ferguson
R Abagyan
M A Lemmon
A Aronheim
E Y Skolnik
New York University · USUniversity of Pennsylvania · USTechnion – Israel Institute of Technology · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Phosphatidylinositol 3-kinase (PI3K) mediates a variety of cellular responses by generating PtdIns(3,4)P2 and PtdIns(3,4,5)P3. These 3-phosphoinositides then function directly as second messengers to activate downstream signaling molecules by binding pleckstrin homology (PH) domains in these signaling molecules. We have established a novel assay in the yeast Saccharomyces cerevisiae to identify proteins that bind PtdIns(3,4)P2 and PtdIns(3,4,5)P3 in vivo which we have called TOPIS (Targets of PI3K Identification System). The assay uses a plasma membrane-targeted Ras to complement a temperature-sensitive CDC25 Ras exchange factor in yeast. Coexpression of PI3K and a fusion protein of activated Ras joined to a PH domain known to bind PtdIns(3,4)P2 (AKT) or PtdIns(3,4,5)P3 (BTK) rescues yeast growth at the non-permissive temperature of 37 degreesC. Using this assay, we have identified several amino acids in the beta1-beta2 region of PH domains that are critical for high affinity binding to PtdIns(3,4)P2 and/or PtdIns(3,4,5)P3, and we have proposed a structural model for how these PH domains might bind PI3K products with high affinity. From these data, we derived a consensus sequence which predicts high-affinity binding to PtdIns(3, 4)P2 and/or PtdIns(3,4,5)P3, and we have identified several new PH domain-containing proteins that bind PI3K products, including Gab1, Dos, myosinX, and Sbf1. Use of this assay to screen for novel cDNAs which rescue yeast at the non-permissive temperature should provide a powerful approach for uncovering additional targets of PI3K.

Indexed as

PhosphoproteinsAmino Acid SequenceBlood ProteinsCell MembraneConsensus SequenceConserved SequenceFungal ProteinsModels, MolecularMutationPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesProtein Bindingras ProteinsRecombinant Fusion ProteinsSaccharomyces cerevisiaeSecond Messenger SystemsBlood ProteinsFungal Proteinsphosphatidylinositol 3,4,5-triphosphatephosphatidylinositol 3,4-diphosphatePhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesPhosphoproteinsplatelet protein P47ras ProteinsRecombinant Fusion Proteins

Identifiers

PMID9736615
PMCPMC1170863
OpenAlexW2141206157

What Socratic 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 Socratic graph.