ArticleOncogene1999
Effect of SB 203580 on the activity of c-Raf in vitro and in vivo.
Article in Oncogene, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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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.
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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.
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Who cites it
40 citing papers in PubMed, 150 citations in OpenAlex.
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- A systematic analysis of signaling reactivation and drug resistance.Cell reports · 2021Article
- RAS Function in cancer cells: translating membrane biology and biochemistry into new therapeutics.The Biochemical journal · 2020Review
- Of Mice and Monkeys: Neuroprotective Efficacy of the p38 Inhibitor BIRB 796 Depends on Model Duration in Experimental Glaucoma.Scientific reports · 2020Article
- Chemoattractant concentration-dependent tuning of ERK signaling dynamics in migrating neutrophils.Science signaling · 2016Article
- Promotion of metastasis of thyroid cancer cells via NRP-2-mediated induction.Oncology letters · 2016Article
- Evaluating the Role of p38 MAPK in the Accelerated Cell Senescence of Werner Syndrome Fibroblasts.Pharmaceuticals (Basel, Switzerland) · 2016Article
- Registered report: Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF.eLife · 2016Article
- Registered report: RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth.eLife · 2016Article
- Ten things you should know about protein kinases: IUPHAR Review 14.British journal of pharmacology · 2015Review
- Article
- Inhibition of neuronal p38α, but not p38β MAPK, provides neuroprotection against three different neurotoxic insults.Journal of molecular neuroscience : MN · 2015Article
- Crosstalk between mitogen-activated protein kinases and mitochondria in cardiac diseases: therapeutic perspectives.Pharmacology & therapeutics · 2014Review
- Combating Adaptation to Cyclic Stretching By Prolonging Activation of Extracellular Signal-Regulated Kinase.Cellular and molecular bioengineering · 2013Article
- Inhibitors that stabilize a closed RAF kinase domain conformation induce dimerization.Nature chemical biology · 2013Article
- Murine cytomegalovirus (MCMV) infection upregulates P38 MAP kinase in aortas of Apo E KO mice: a molecular mechanism for MCMV-induced acceleration of atherosclerosis.Journal of cardiovascular translational research · 2013Article
- BDNF alters ERK/p38 MAPK activity ratios to promote differentiation in growth plate chondrocytes.Molecular endocrinology (Baltimore, Md.) · 2012Article
- MK2 Regulates Ras Oncogenesis through Stimulating ROS Production.Genes & cancer · 2012Article
- Binding of BIS like and other ligands with the GSK-3β kinase: a combined docking and MM-PBSA study.Journal of molecular modeling · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The inhibition of SAPK2a/p38 (a mitogen activated protein (MAP) kinase family member) by SB 203580 depends on the presence of threonine at residue 106. Nearly all other protein kinases are insensitive to this drug because a more bulky residue occupies this site (Eyers et al., 1998). Raf is one of the few protein kinases that possesses threonine at this position, and we show that SB 203580 inhibits c-Raf with an IC50 of 2 microM in vitro. However, SB 203580 does not suppress either growth factor or phorbol ester-induced activation of the classical MAP kinase cascade in mammalian cells. One of the reasons for this is that SB 203580 also triggers a remarkable activation of c-Raf in vivo (when measured in the absence of the drug). The SB 203580-induced activation of c-Raf occurs without any increase in the GTP-loading of Ras, is not prevented by inhibitors of the MAPK cascade, protein kinase C or phosphatidylinositide 3-kinase, and is not triggered by the binding of this drug to SAPK2a/p38. The paradoxical activation of c-Raf by SB 203580 (and by another structurally unrelated c-Raf inhibitor) suggests that inhibitors of the kinase activity of c-Raf may not be effective as anti-cancer drugs.
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Registered trials
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.