ArticleMolecular & cellular proteomics : MCP2010
High content screening for inhibitors of protein interactions and post-translational modifications in primary cells by proximity ligation.
Article in Molecular & cellular proteomics : MCP, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 73 citations in OpenAlex.
- Proximity Ligation Assay to Detect Protein-Protein Interaction in Cancer Cells.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Detecting Disruption of HER2 Membrane Protein Organization in Cell Membranes with Nanoscale Precision.ACS sensors · 2024Article
- Targeting the interaction of GABABrain pathology (Zurich, Switzerland) · 2023Article
- Protein phosphatase 2A regulation of GABAFrontiers in molecular neuroscience · 2022Article
- Proximity ligation assay: an ultrasensitive method for protein quantification and its applications in pathogen detection.Applied microbiology and biotechnology · 2021Review
- PTPIP51 crosslinks the NFκB signaling and the MAPK pathway in SKBR3 cells.Future science OA · 2020Article
- Development and Optimization of a Miniaturized Western Blot-Based Screening Platform to Identify Regulators of Post-Translational Modifications.High-throughput · 2019Article
- HiPLA: High-throughput imaging proximity ligation assay.Methods (San Diego, Calif.) · 2019Article
- CaMolecular neurobiology · 2019Article
- Crosstalks of the PTPIP51 interactome revealed in Her2 amplified breast cancer cells by the novel small molecule LDC3/Dynarrestin.PloS one · 2019Article
- Regulation of Sox2 and stemness by nicotine and electronic-cigarettes in non-small cell lung cancer.Molecular cancer · 2018Article
- Effectiveness of EGFR/HER2-targeted drugs is influenced by the downstream interaction shifts of PTPIP51 in HER2-amplified breast cancer cells.Oncogenesis · 2018Article
- Lys-63-linked Ubiquitination of γ-Aminobutyric Acid (GABA), Type B1, at Multiple Sites by the E3 Ligase Mind Bomb-2 Targets GABAB Receptors to Lysosomal Degradation.The Journal of biological chemistry · 2016Article
- Phosphorylation state-dependent modulation of spinal glycine receptors alleviates inflammatory pain.The Journal of clinical investigation · 2016Article
- Identification of cytotoxic agents disrupting synovial sarcoma oncoprotein interactions by proximity ligation assay.Oncotarget · 2016Article
- Inhibitors of the apurinic/apyrimidinic endonuclease 1 (APE1)/nucleophosmin (NPM1) interaction that display anti-tumor properties.Molecular carcinogenesis · 2016Article
- HER-3 targeting alters the dimerization pattern of ErbB protein family members in breast carcinomas.Oncotarget · 2016Article
- Current Approaches Toward Quantitative Mapping of the Interactome.Frontiers in genetics · 2016Article
- Proximity assays for sensitive quantification of proteins.Biomolecular detection and quantification · 2015Review
- Increasing the Content of High-Content Screening: An Overview.Journal of biomolecular screening · 2014Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cost of developing new drugs is a major obstacle for pharmaceutical companies and academia with many drugs identified in the drug discovery process failing approval for clinical use due to lack of intended effect or because of severe side effects. Since the early 1990 s, high throughput screening of drug compounds has increased enormously in capacity but has not resulted in a higher success rate of the identified drugs. Thus, there is a need for methods that can identify biologically relevant compounds and more accurately predict in vivo effects early in the drug discovery process. To address this, we developed a proximity ligation-based assay for high content screening of drug effects on signaling pathways. As a proof of concept, we used the assay to screen through a library of previously identified kinase inhibitors, including six clinically used tyrosine kinase inhibitors, to identify compounds that inhibited the platelet-derived growth factor (PDGF) receptor beta signaling pathway in stimulated primary human fibroblasts. Thirteen of the 80 compounds were identified as hits, and the dose responses of these compounds were measured. The assay exhibited a very high Z' factor (0.71) and signal to noise ratio (11.7), demonstrating excellent ability to identify compounds interfering with the specific signaling event. A comparison with regular immunofluorescence detection of phosphorylated PDGF receptor demonstrated a far superior ability by the in situ proximity ligation assay to reveal inhibition of receptor phosphorylation. In addition, inhibitor-induced perturbation of protein-protein interactions of the PDGF signaling pathway could be quantified, further demonstrating the usefulness of the assay in drug discovery.
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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.