| First Author | Dugan MP | Year | 2023 |
| Journal | Mol Cell Proteomics | Volume | 22 |
| Issue | 4 | Pages | 100522 |
| PubMed ID | 36863607 | Mgi Jnum | J:337737 |
| Mgi Id | MGI:7506173 | Doi | 10.1016/j.mcpro.2023.100522 |
| Citation | Dugan MP, et al. (2023) Chemical Genetic Identification of PKC Epsilon Substrates in Mouse Brain. Mol Cell Proteomics 22(4):100522 |
| abstractText | PKC epsilon (PKCepsilon) 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 PKCepsilon could reveal additional targets and strategies for interfering with PKCepsilon signaling. We used a chemical genetic screen combined with mass spectrometry to identify direct substrates of PKCepsilon 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-L1000, STRING, GeneFriends, and GeneMAINA predicted interactions between these putative substrates and PKCepsilon 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 PKCepsilon substrates, many of which are novel, for future investigation to determine the role of PKCepsilon signaling in alcohol responses, anxiety, responses to stress, and other related behaviors. |
