ArticleProceedings of the National Academy of Sciences of the United States of America2003
An efficient proteomics method to identify the cellular targets of protein kinase inhibitors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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102 citing papers in PubMed, 333 citations in OpenAlex.
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- A Constellation of Fluorescent Biosensors to Illuminate the Galaxy of Protein Kinases.Chembiochem : a European journal of chemical biology · 2026Review
- α-Viniferin Induces Intrinsic Apoptosis in Triple-Negative Breast Cancer Cells and Synergizes With SB203580 Independently of p38 Mitogen-Activated Protein Kinase.Journal of breast cancer · 2026Article
- Targeting p38α in cancer: challenges, opportunities, and emerging strategies.Molecular oncology · 2026Review
- Structure-activity Relationship for Diarylpyrazoles as Inhibitors of the Fungal Kinase Yck2.bioRxiv : the preprint server for biology · 2025Article
- Dexmedetomidine alleviates blood-brain barrier disruption in rats after cerebral ischemia-reperfusion by suppressing JNK and p38 MAPK signaling.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2024Article
- Review
- Affinity-based profiling of endogenous phosphoprotein phosphatases by mass spectrometry.Nature protocols · 2021Review
- Stress-activated kinases as therapeutic targets in pancreatic cancer.World journal of gastroenterology · 2021Review
- Diversity and versatility of p38 kinase signalling in health and disease.Nature reviews. Molecular cell biology · 2021Review
- Turning liabilities into opportunities: Off-target based drug repurposing in cancer.Seminars in cancer biology · 2021Review
- The sex-specific role of p38 MAP kinase in CNS autoimmunity is regulated by estrogen receptor alpha.Journal of neuroimmunology · 2020Article
- A temperature-dependent conformational shift in p38α MAPK substrate-binding region associated with changes in substrate phosphorylation profile.The Journal of biological chemistry · 2019Article
- A Quantitative Chemical Proteomic Strategy for Profiling Phosphoprotein Phosphatases from Yeast to Humans.Molecular & cellular proteomics : MCP · 2018Article
- Proteome-Wide Structural Biology: An Emerging Field for the Structural Analysis of Proteins on the Proteomic Scale.Journal of proteome research · 2018Review
- The p38α MAPK Deletion in Oligodendroglia does not Attenuate Myelination Defects in a Mouse Model of Periventricular Leukomalacia.Neuroscience · 2018Article
- Stress-Activated Protein Kinases in Spinal Cord Injury: Focus on Roles of p38.International journal of molecular sciences · 2018Review
- Direct and tunable modulation of protein levels in rice and wheat with a synthetic small molecule.Plant biotechnology journal · 2018Article
- Polypharmacology-based ceritinib repurposing using integrated functional proteomics.Nature chemical biology · 2017Article
- Anti-inflammatory roles of p38α MAPK in macrophages are context dependent and require IL-10.Journal of leukocyte biology · 2017Article
42 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small molecule inhibitors of protein kinases are widely used in signal transduction research and are emerging as a major class of drugs. Although interpretation of biological results obtained with these reagents critically depends on their selectivity, efficient methods for proteome-wide assessment of kinase inhibitor selectivity have not yet been reported. Here, we address this important issue and describe a method for identifying targets of the widely used p38 kinase inhibitor SB 203580. Immobilization of a suitable SB 203580 analogue and thoroughly optimized biochemical conditions for affinity chromatography permitted the dramatic enrichment and identification of several previously unknown protein kinase targets of SB 203580. In vitro kinase assays showed that cyclin G-associated kinase (GAK) and CK1 were almost as potently inhibited as p38alpha whereas RICK [Rip-like interacting caspase-like apoptosis-regulatory protein (CLARP) kinase/Rip2/CARDIAK] was even more sensitive to inhibition by SB 203580. The cellular kinase activity of RICK, a known signal transducer of inflammatory responses, was already inhibited by submicromolar concentrations of SB 203580 in intact cells. Therefore, our results warrant a reevaluation of the vast amount of data obtained with SB 203580 and might have significant implications on the development of p38 inhibitors as antiinflammatory drugs. Based on the procedures described here, efficient affinity purification techniques can be developed for other protein kinase inhibitors, providing crucial information about their cellular modes of action.
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