Evidence map›Paper›PMID 12835716›Full record

ReviewLeukemia2003

Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention.

F Chang, L S Steelman, J T Lee, J G Shelton, P M Navolanic, W L Blalock, R A Franklin, J A McCubrey

Abstract readReview
PubMed Publisher
In one paragraph

Review in Leukemia, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 309 papers.

0numbers the graph read from it
0cells of the map it votes in
309citing papers in PubMed
15.5field-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

309 citing papers in PubMed, 732 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Synergistic roles of NFATc1 and c-Jun in immunomodulation.Biochemistry and biophysics reports · 2025
    Review
  10. Article
  11. Ras-mediated dynamic and biphasic regulation of cell migration.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review

249 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

8 authors at 2 institutions in 1 country.

F ChangDepartment of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA.
L S Steelman
J T Lee
J G Shelton
P M Navolanic
W L Blalock
R A Franklin
J A McCubrey
East Carolina University · USUniversity of Florida · US

Funding

Ras/Raf &PI3K/Akt Induced Breast Cancer Drug ResistanceR01CA098195 · NCI · EAST CAROLINA UNIVERSITY · PI MC CUBREY, JAMES A · 2003 to 2007
$1.5M
MECHANISMS OF TRANSFORMATION OF HEMOPOIETIC CELLSR01CA051025 · NCI · EAST CAROLINA UNIVERSITY · PI MC CUBREY, JAMES A · 1992 to 2001
$361k
NCI NIH HHS R01 CA 51025NCI NIH HHS R01 CA 98195
6 · The paper itself

Abstract

The Ras/Raf/Mitogen-activated protein kinase/ERK kinase (MEK)/extracellular-signal-regulated kinase (ERK) cascade couples signals from cell surface receptors to transcription factors, which regulate gene expression. Depending upon the stimulus and cell type, this pathway can transmit signals, which result in the prevention or induction of apoptosis or cell cycle progression. Thus, it is an appropriate pathway to target for therapeutic intervention. This pathway becomes more complex daily, as there are multiple members of the kinase and transcription factor families, which can be activated or inactivated by protein phosphorylation. The diversity of signals transduced by this pathway is increased, as different family members heterodimerize to transmit different signals. Furthermore, additional signal transduction pathways interact with the Raf/MEK/ERK pathway to regulate positively or negatively its activity, or to alter the phosphorylation status of downstream targets. Abnormal activation of this pathway occurs in leukemia because of mutations at Ras as well as genes in other pathways (eg PI3K, PTEN, Akt), which serve to regulate its activity. Dysregulation of this pathway can result in autocrine transformation of hematopoietic cells since cytokine genes such as interleukin-3 and granulocyte/macrophage colony-stimulating factor contain the transacting binding sites for the transcription factors regulated by this pathway. Inhibitors of Ras, Raf, MEK and some downstream targets have been developed and many are currently in clinical trials. This review will summarize our current understanding of the Ras/Raf/MEK/ERK signal transduction pathway and the downstream transcription factors. The prospects of targeting this pathway for therapeutic intervention in leukemia and other cancers will be evaluated.

Indexed as

Drug DesignEnzyme InhibitorsHumansMAP Kinase Signaling SystemProto-Oncogene Proteins c-rafras ProteinsReceptors, CytokineTranscription FactorsEnzyme InhibitorsProto-Oncogene Proteins c-rafras ProteinsReceptors, CytokineTranscription Factors

Identifiers

PMID12835716
OpenAlexW2075091190

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.