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Advances in chemical proteomic evaluation of lipid kinases—DAG kinases as a case study
Institution:1. Department of Chemistry, University of Virginia, Charlottesville, VA 22904, United States;2. Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22908, United States;3. Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, United States;4. University of Virginia Cancer Center, University of Virginia, Charlottesville, VA 22903, USA;1. The Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA;2. The Department of Biophysics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;3. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA;4. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;1. Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA;2. Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA;3. Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA;4. Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA;1. Dept. of Physiology & Pharmacology, Oregon Health and Science University (OHSU), Portland, OR, USA;2. European Molecular Biology Laboratory (EMBL), Cell Biology and Biophysics Unit, 69117 Heidelberg, Germany
Abstract:Advancements in chemical proteomics and mass spectrometry lipidomics are providing new opportunities to understand lipid kinase activity, specificity, and regulation on a global cellular scale. Here, we describe recent developments in chemical biology of lipid kinases with a focus on those members that phosphorylate diacylglycerols. We further discuss future implications of how these mass spectrometry–based approaches can be adapted for studies of additional lipid kinase members with the aim of bridging the gap between protein and lipid kinase–focused investigations.
Keywords:Kinase  Phosphorylation  Lipid  Diacylglycerol  Phosphoinositide  Kinome  Signaling  Chemical proteomics  Activity-based protein profiling  Mass spectrometry  Lipidomics  Sulfonyl triazoles  Sulfonyl fluorides  SuTEx  SuFEx  Phosphatidic acid
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