ArticleMolecular & cellular proteomics : MCP2018
Specificity of Phosphorylation Responses to Mitogen Activated Protein (MAP) Kinase Pathway Inhibitors in Melanoma Cells.
Article in Molecular & cellular proteomics : MCP, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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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23 citing papers in PubMed, 35 citations in OpenAlex.
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- Role of histone-lysine N-methyltransferase 2D (KMT2D) in MEK-ERK signaling-mediated epigenetic regulation: a phosphoproteomics perspective.Frontiers in bioinformatics · 2025Article
- Preclinical evidence for employing MEK inhibition in NRAS mutated pediatric gastroenteropancreatic neuroendocrine-like tumors.Translational oncology · 2024Article
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- Dynamic equilibria in protein kinases.Current opinion in structural biology · 2021Review
- Probing the signaling requirements for naive human pluripotency by high-throughput chemical screening.Cell reports · 2021Article
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- Hyperphosphorylation of HDAC2 promotes drug resistance in a novel dual drug resistant mouse melanoma cell line model: anAmerican journal of cancer research · 2021Article
- Identification of the Host Substratome ofFrontiers in cell and developmental biology · 2021Article
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- The effect of MEK1/2 inhibitors on cisplatin-induced acute kidney injury (AKI) and cancer growth in mice.Cellular signalling · 2020Article
- Quantitative phosphoproteomic analysis identifies the potential therapeutic target EphA2 for overcoming sorafenib resistance in hepatocellular carcinoma cells.Experimental & molecular medicine · 2020Article
- DECO: decompose heterogeneous population cohorts for patient stratification and discovery of sample biomarkers using omic data profiling.Bioinformatics (Oxford, England) · 2019Article
- Clinical protein science in translational medicine targeting malignant melanoma.Cell biology and toxicology · 2019Article
- Activation loop dynamics are controlled by conformation-selective inhibitors of ERK2.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Functional divergence caused by mutations in an energetic hotspot in ERK2.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Article
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Authors and funding
7 authors at 1 institution in 3 countries.
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Abstract
The BRAF-MKK1/2-ERK1/2 pathway is constitutively activated in response to oncogenic mutations of BRAF in many cancer types, including melanoma. Although small molecules that inhibit oncogenic BRAF and MAP kinase kinase (MKK)1/2 have been successful in clinical settings, resistance invariably develops. High affinity inhibitors of ERK1/2 have been shown in preclinical studies to bypass the resistance of melanoma and colon cancer cells to BRAF and MKK1/2 inhibitors, and are thus promising additions to current treatment protocols. But still unknown is how molecular responses to ERK1/2 inhibitors compare with inhibitors currently in clinical use. Here, we employ quantitative phosphoproteomics to evaluate changes in phosphorylation in response to the ERK inhibitors, SCH772984 and GDC0994, and compare these to the clinically used MKK1/2 inhibitor, trametinib. Combined with previous studies measuring phosphoproteomic responses to the MKK1/2 inhibitor, selumetinib, and the BRAF inhibitor, vemurafenib, the outcomes reveal key insights into pathway organization, phosphorylation specificity and off-target effects of these inhibitors. The results demonstrate linearity in signaling from BRAF to MKK1/2 and from MKK1/2 to ERK1/2. They identify likely targets of direct phosphorylation by ERK1/2, as well as inhibitor off-targets, including an off-target regulation of the p38α mitogen activated protein kinase (MAPK) pathway by the MKK1/2 inhibitor, trametinib, at concentrations used in the literature but higher than
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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.