Evidence map›Paper›PMID 8195713›Full record

ArticleThe Journal of experimental medicine1994

Negative regulation of p120GAP GTPase promoting activity by p210bcr/abl: implication for RAS-dependent Philadelphia chromosome positive cell growth.

T Skorski, P Kanakaraj, D H Ku, M Nieborowska-Skorska, E Canaani, G Zon, B Perussia, B Calabretta

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
4.7field-weighted citation impact, top 4% 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

25 citing papers in PubMed, 104 citations in OpenAlex.

  1. Article
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  13. Review
  14. Mechanisms of transformation by the BCR/ABL oncogene.International journal of hematology · 2001
    Review
  15. Article
  16. Tyrosine phosphorylation of p62dok by p210bcr-abl inhibits RasGAP activity.Proceedings of the National Academy of Sciences of the United States of America · 2000
    Article
  17. Article
  18. Article
  19. Article
  20. BCR/ABL-mediated leukemogenesis requires the activity of the small GTP-binding protein Rac.Proceedings of the National Academy of Sciences of the United States of America · 1998
    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

8 authors at 1 institution in 1 country.

T SkorskiDepartment of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
P Kanakaraj
D H Ku
M Nieborowska-Skorska
E Canaani
G Zon
B Perussia
B Calabretta
Thomas Jefferson University · US

Funding

RECEPTORS FOR IMMUNOGLOBULIN G ON LEUKOCYTESR01CA037155 · NCI · WISTAR INSTITUTE · PI PERUSSIA, BICE · 1985 to 1997
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ALTERED GROWTH REGULATION IN HUMAN LEUKEMIAR01CA046782 · NCI · THOMAS JEFFERSON UNIVERSITY · PI CALABRETTA, BRUNO · 1988 to 1999
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NCI NIH HHS CA-37155NCI NIH HHS CA45826NCI NIH HHS CA-46782
6 · The paper itself

Abstract

The p210bcr/abl tyrosine kinase appears to be responsible for initiating and maintaining the leukemic phenotype in chronic myelogenous leukemia (CML) patients. p21ras-p120GAP interactions play a central role in transducing mitogenic signals. Therefore, we investigated whether p21ras and p120GAP are regulated by p210bcr/abl, and whether this activation is functionally significant for CML cell proliferation. We report that transient expression of p210bcr/abl in fibroblast-like cells induces simultaneous activation of p21ras and inhibition of GTPase-promoting activity of p120GAP, and confirm these data showing that downregulation of p210bcr/abl expression in CML cells with bcr/abl antisense oligodeoxynucleotides induces both inhibition of p21ras activation and stimulation of GTPase-promoting activity of p120GAP. Tyrosine phosphorylation of two p120GAP-associated proteins, p190 and p62, which may affect p120GAP activity, also depends on p210bcr/abl tyrosine kinase expression. Direct dependence of these effects on the kinase activity is proven in experiments in which expression of c-MYB protein in fibroblast-like cells or downregulation of c-MYB expression resulting in analogous inhibition of CML cell proliferation does not result in the same changes. Use of specific antisense oligodeoxynucleotides to downregulate p21ras expression revealed a requirement for functional p21ras in the proliferation of Philadelphia chromosome-positive CML primary cells. Thus, the p210bcr/abl-dependent regulation of p120GAP activity is responsible, in part, for the maintenance of p21ras in the active GTP-bound form, a crucial requirement for CML cell proliferation.

Indexed as

Philadelphia ChromosomeBase SequenceCell DivisionCell LineChromosomes, Human, Pair 15Chromosomes, Human, Pair 17Chromosomes, Human, Pair 22Chromosomes, Human, Pair 9Fusion Proteins, bcr-ablGene Expression Regulation, NeoplasticGTPase-Activating ProteinsGTP PhosphohydrolasesHomeostasisHumansLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMolecular Sequence DataFusion Proteins, bcr-ablGTPase-Activating ProteinsGTP PhosphohydrolasesHRAS protein, humanOligonucleotides, AntisenseProteinsProto-Oncogene Proteins p21(ras)ras GTPase-Activating Proteins

Identifiers

PMID8195713
PMCPMC2191514
OpenAlexW2128792199

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.