Chemical Genetic Identification of PKC Epsilon Substrates in Mouse Brain
| Autor: | Michael P. Dugan, Laura B. Ferguson, Nicholas T. Hertz, Robert J. Chalkley, Alma L. Burlingame, Kevan M. Shokat, Peter J. Parker, Robert O. Messing |
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| Rok vydání: | 2023 |
| Předmět: |
Biochemistry & Molecular Biology
Alcohol Drinking Protein Kinase C-epsilon Biochemistry & Proteomics Biochemistry Basic Behavioral and Social Science Analytical Chemistry Signalling & Oncogenes Mice Alcohol Use and Health Substance Misuse Behavioral and Social Science Genetics Animals 2.1 Biological and endogenous factors Aetiology Molecular Biology Chemical Biology & High Throughput Ethanol Research Neurosciences Brain Cell Biology Brain Disorders Alcoholism Good Health and Well Being Cell Cycle & Chromosomes Mental health Signal Transduction |
| Zdroj: | Molecular & cellular proteomics : MCP, vol 22, iss 4 Mol Cell Proteomics |
| Popis: | Protein kinase C epsilon (PKCε) plays important roles in behavioral responses to alcohol and in anxiety-like behavior in rodents, making it a potential drug target for reducing alcohol consumption and anxiety. Identifying signals downstream of PKCε could reveal additional targets and strategies for interfering with PKCε signaling. We used a chemical genetic screen combined with mass spectrometry to identify direct substrates of PKCε in mouse brain, and validated findings for 39 of them using peptide arrays and in vitro kinase assays. Prioritizing substrates with several public databases such as LINCS-1000, STRING, GeneFriends, and GeneMAINA, predicted interactions between these putative substrates and PKCε, and identified substrates associated with alcohol-related behaviors, actions of benzodiazepines, and chronic stress. The 39 substrates could be broadly classified in three functional categories: cytoskeletal regulation, morphogenesis, and synaptic function. These results provide a list of brain PKCε substrates, many of which are novel, for future investigation to determine the role of PKCε signaling in alcohol responses, anxiety, responses to stress, and other related behaviors. |
| Databáze: | OpenAIRE |
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