The Ras-Raf-MEK-ERK Pathway in the Treatment of Cancer

@article{Hilger2002TheRP,
  title={The Ras-Raf-MEK-ERK Pathway in the Treatment of Cancer},
  author={Ralf Axel Hilger and Max Ernst Scheulen and Dirk Strumberg},
  journal={Oncology Research and Treatment},
  year={2002},
  volume={25},
  pages={511 - 518}
}
The mitogen activated protein kinases (MAPKs) are conserved proteins that regulate cell growth, division and death. Although activated in the cytosol, the MAPKs translocate to the nucleus upon activation and phosphorylate a large number of nuclear proteins. Investigating how Ras transmits extracellular growth signals, the MAPK pathway has emerged as the crucial route between membrane-bound Ras and the nucleus. The MAPK pathway represents a cascade of phosphorylation events including three… Expand
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References

SHOWING 1-10 OF 101 REFERENCES
Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions.
  • W. Kolch
  • Chemistry, Medicine
  • The Biochemical journal
  • 2000
TLDR
The role of protein-protein interactions in the regulation of this pathway is focused on, and how they contribute to co-ordinate activation steps, subcellular redistribution, substrate phosphorylation and cross-talk with other signalling pathways. Expand
Transcriptional regulation by MAP kinases
  • Roger J. Davis
  • Biology, Medicine
  • Molecular reproduction and development
  • 1995
TLDR
The MAP kinase pathway represents a significant mechanism of signal transduction by growth factor receptors from the cell surface to the nucleus that results in the regulation of gene expression. Expand
Paradoxical activation of Raf by a novel Raf inhibitor.
TLDR
Raf appears to suppress its own activation by a novel feedback loop, such that inhibition is always counterbalanced by reactivation, implying that some agonists reported to trigger the cellular activation of c-Raf might actually be inhibitors of this enzyme, and that compounds which inhibit the kinase activity of Raf might not be useful as anticancer drugs. Expand
Signal transduction through MAP kinase cascades.
TLDR
The chapter explores the cellular substrates of MAP kinases, wherein it discusses about protein kinase substrates for MAPKS, nuclear transcription factors, signaling components, and cytoskeletal proteins. Expand
Mitogen-Activated Protein Kinases: Specific Messages from Ubiquitous Messengers
TLDR
Recent findings are described that provide insight into ways that the regulation, structure, and localization of MAPKs and the participation of adapters and scaffolds can help determine biological outcomes. Expand
Transformation of mammalian cells by constitutively active MAP kinase kinase.
TLDR
It is found that constitutive activation of MAPKK is sufficient to promote cell transformation and is associated with highly tumorigenic in nude mice. Expand
Analysis of the transcriptional program induced by Raf in epithelial cells
TLDR
Autocrine activation of the EGF receptor was shown to be responsible for the ability of Raf activation to protect these cells from apoptosis induced by detachment of cells from extracellular matrix (anoikis), which is a critical component of the transformed phenotype. Expand
The primary structure of MEK, a protein kinase that phosphorylates the ERK gene product.
TLDR
The structure of this protein kinase, denoted MEK1, was elucidated from a complementary DNA sequence and shown to be a protein of 393 amino acids that is related most closely in size and sequence to the product encoded by the Schizosaccharomyces pombe byr1 gene. Expand
Isotype-specific functions of Raf kinases.
TLDR
Since Raf is part of a multiprotein complex and protein-protein interactions are important for Raf signaling, it is proposed that isotypes-specific functions can be achieved by isotype-restricted protein binding and candidates for such Raf-isoform-specific interaction partners are identified. Expand
Ras protein farnesyltransferase: A strategic target for anticancer therapeutic development.
TLDR
It follows that inhibiting FTase would prevent Ras from maturing into its biologically active form, and FTase is of considerable interest as a potential therapeutic target. Expand
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