title: Quantitative proteomics reveals protein kinases and phosphatases in the individual phases of contextual fear conditioning in the C57BL/6J mouse.
abstract: A series of protein kinases and phosphatases (PKPs) have been linked to contextual fear conditioning (cFC) but information is mainly derived from immunochemical studies. It was therefore decided to use an explorative label-free quantitative proteomics approach to concomitantly determine PKPs in hippocampi of mice in the individual phases of cFC. C57BL/6J mice were divided into four groups: three training groups representing the acquisition, consolidation and retrieval phases of cFC and a foot shock control group. Using this approach we identified 32 protein kinases or phosphatases/phosphatase subunits with significantly changed protein levels in one or more training groups as compared to foot shock control. These include members of PKP signalling modules of mitogen-activated protein kinase (MAP3K10, RAF1, KSR2), Ca2+/calmodulin-dependent protein kinase (CaMKIIα, DAPK1), protein kinase C (PRKCD) and protein phosphatases 1, 2A, 2B(3) previously implicated in various learning paradigms. In addition, our analysis showed protein kinases WNK1, LYN, VRK1, ABL1, CDK4, CDKL3, SgK223 and ADCK1, and protein phosphatases PTPRF, ACP1, DNAJC6, SSH2 and UBASH3B that have not been directly linked to fear memory processes so far. Determination of PKPs in the individual cFC phases represents a valuable resource for interpretation of previous and design of future studies on PKPs in memory mechanisms.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Roman
authors.initials: R
authors.lastname: Šmidák
authors.affiliation: Department of Analytical Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Rupert Laurenz
authors.initials: RL
authors.lastname: Mayer
authors.affiliation: Department of Analytical Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bileck
authors.affiliation: Department of Analytical Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Christopher
authors.initials: C
authors.lastname: Gerner
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Diana
authors.initials: D
authors.lastname: Mechtcheriakova
authors.affiliation: Faculty of Science Genetics and Molecular Neurobiology, Magdeburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Stork
authors.affiliation: Department of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria. Electronic address: gert.lubec@uniwie.ac.at.
authors.forename: Gert
authors.initials: G
authors.lastname: Lubec
authors.affiliation: Department of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D040901:Proteomics
chemical_list: D011494:Protein Kinases; D010744:Phosphoric Monoester Hydrolases
keywords: Contextual fear conditioning; Hippocampus; Label-free MS quantitative analysis; Protein kinases; Protein phosphatases