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Chemical genetic identification of protein kinase C epsilon substrates in mouse brain

ABSTRACT: Protein kinase C epsilon 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 PKC Epsilon could reveal additional targets and strategies for interfering with PKC Epsilon signaling. We used a chemical genetic screen combined with mass spectrometry to identify direct substrates of PKC Epsilon, and validated findings for 43 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 PKC Epsilon, and identified substrates associated with alcohol-related behaviors, actions of benzodiazepines, and chronic stress. The 43 substrates could be broadly classified in three functional categories: cytoskeletal regulation, morphogenesis, and synaptic release. These results provide a list of brain PKC Epsilon substrates, many of which are novel, for future investigation to determine the role of PKC Epsilon signaling in alcohol responses, anxiety, responses to stress, and other related behaviors.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (ncbitaxon:9606) Mus Musculus (ncbitaxon:10090)

SUBMITTER: Robert O. Messing

PROVIDER: MSV000089659 | MassIVE | Wed Jun 15 14:16:00 BST 2022

REPOSITORIES: MassIVE

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