ArticleProteomics2015
Effects of MEK inhibitors GSK1120212 and PD0325901 in vivo using 10-plex quantitative proteomics and phosphoproteomics.
Article in Proteomics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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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Who cites it
45 citing papers in PubMed, 70 citations in OpenAlex.
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- E-cadherin interacts with EGFR resulting in hyper-activation of ERK in multiple models of breast cancer.Oncogene · 2024Article
- A Novel PDK1/MEK Dual Inhibitor Induces Cytoprotective Autophagy via the PDK1/Akt Signaling Pathway in Non-Small Cell Lung Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Article
- The Emerging Burden of Genetic Instability and Mutation in Melanoma: Role of Molecular Mechanisms.Cancers · 2022Article
- A Genome-Wide Screen Identifies PDPK1 as a Target to Enhance the Efficacy of MEK1/2 Inhibitors in NRAS Mutant Melanoma.Cancer research · 2022Article
- Effects of ex vivo blood anticoagulation and preanalytical processing time on the proteome content of platelets.Journal of thrombosis and haemostasis : JTH · 2022Article
- Drug Repurposing by Tumor Tissue Editing.Frontiers in oncology · 2022Review
- Advances in quantitative high-throughput phosphoproteomics with sample multiplexing.Proteomics · 2021Review
- Serine-Threonine Kinase TAO3-Mediated Trafficking of Endosomes Containing the Invadopodia Scaffold TKS5α Promotes Cancer Invasion and Tumor Growth.Cancer research · 2021Article
- Gene dosage manipulation alleviates manifestations of hereditaryScience translational medicine · 2020Article
- Optimized Workflow for Multiplexed Phosphorylation Analysis of TMT-Labeled Peptides Using High-Field Asymmetric Waveform Ion Mobility Spectrometry.Journal of proteome research · 2020Article
- Identification of PKCα-dependent phosphoproteins in mouse retina.Journal of proteomics · 2019Article
- Multiomics Profiling Establishes the Polypharmacology of FDA-Approved CDK4/6 Inhibitors and the Potential for Differential Clinical Activity.Cell chemical biology · 2019Article
- Tissue-Specific Oncogenic Activity of KRASCancer discovery · 2019Article
- A Review on Quantitative Multiplexed Proteomics.Chembiochem : a European journal of chemical biology · 2019Review
- An Internal Standard for Assessing Phosphopeptide Recovery from Metal Ion/Oxide Enrichment Strategies.Journal of the American Society for Mass Spectrometry · 2018Article
- Streamlined Tandem Mass Tag (SL-TMT) Protocol: An Efficient Strategy for Quantitative (Phospho)proteome Profiling Using Tandem Mass Tag-Synchronous Precursor Selection-MS3.Journal of proteome research · 2018Article
- Phosphorylation of Beta-3 adrenergic receptor at serine 247 by ERK MAP kinase drives lipolysis in obese adipocytes.Molecular metabolism · 2018Article
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6 authors at 2 institutions in 1 country.
Funding
Abstract
Multiplexed isobaric tag based quantitative proteomics and phosphoproteomics strategies can comprehensively analyze drug treatments effects on biological systems. Given the role of mitogen-activated protein/extracellular signal-regulated kinase (MEK) signaling in cancer and mitogen-activated protein kinase (MAPK)-dependent diseases, we sought to determine if this pathway could be inhibited safely by examining the downstream molecular consequences. We used a series of tandem mass tag 10-plex experiments to analyze the effect of two MEK inhibitors (GSK1120212 and PD0325901) on three tissues (kidney, liver, and pancreas) from nine mice. We quantified ∼ 6000 proteins in each tissue, but significant protein-level alterations were minimal with inhibitor treatment. Of particular interest was kidney tissue, as edema is an adverse effect of these inhibitors. From kidney tissue, we enriched phosphopeptides using titanium dioxide (TiO2 ) and quantified 10 562 phosphorylation events. Further analysis by phosphotyrosine peptide immunoprecipitation quantified an additional 592 phosphorylation events. Phosphorylation motif analysis revealed that the inhibitors decreased phosphorylation levels of proline-x-serine-proline (PxSP) and serine-proline (SP) sites, consistent with extracellular-signal-regulated kinase (ERK) inhibition. The MEK inhibitors had the greatest decrease on the phosphorylation of two proteins, Barttin and Slc12a3, which have roles in ion transport and fluid balance. Further studies will provide insight into the effect of these MEK inhibitors with respect to edema and other adverse events in mouse models and human patients.
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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.