title: Kinase networks integrate profiles of N-methyl-D-aspartate receptor-mediated gene expression in hippocampus.
abstract: The postsynaptic N-methyl-d-aspartate (NMDA) receptor activates multiple kinases and changes the phosphorylation of many postsynaptic proteins organized in signaling networks. Because the NMDA receptor is known to regulate gene expression, it is important to examine whether networks of kinases control signaling to gene expression. We examined the requirement of multiple kinases and NMDA receptor-interacting proteins for gene expression in mouse hippocampal slices. Protocols that induce long-term depression (LTD) and long-term potentiation (LTP) activated common kinases and overlapping gene expression profiles. Combinations of kinases were required for induction of each gene. Distinct combinations of kinases were required to up-regulate Arc, Npas4, Egr2, and Egr4 following either LTP or LTD protocols. Consistent with the combinatorial data, a mouse mutant model of the human cognition disease gene SAP102, which couples ERK kinase to the NMDA receptor, showed deregulated expression of specific genes. These data support a network model of postsynaptic integration where kinase signaling networks are recruited by differential synaptic activity and control both local synaptic events and activity-dependent gene expression.
authors.affiliation: Genes to Cognition, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom.
authors.forename: Marcelo P
authors.initials: MP
authors.lastname: Coba
authors.forename: Luis M
authors.initials: LM
authors.lastname: Valor
authors.forename: Maksym V
authors.initials: MV
authors.lastname: Kopanitsa
authors.forename: Nurudeen O
authors.initials: NO
authors.lastname: Afinowi
authors.forename: Seth G N
authors.initials: SG
authors.lastname: Grant
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism*; D017774:Long-Term Potentiation; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism; D013997:Time Factors
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D017868:Cyclic AMP-Dependent Protein Kinases