title: Kainate-elicited seizures induce mRNA encoding a CaMK-related peptide: a putative modulator of kinase activity in rat hippocampus.
abstract: By means of differential display techniques, we have previously identified an mRNA transcript whose expression is highly induced in the rat hippocampus by kainate-elicited seizures. Here, we report the cloning of a corresponding cDNA encoding a 55-amino-acid, serine-rich peptide which contains four predicted phosphorylation sites. The peptide was designated CaMK-related peptide (CARP) as it shares significant amino acid sequence identity with part of a novel putative calcium/calmodulin-dependent kinase (CaMK-VI) that was also cloned in this study. It appears that CARP and CaMK-VI are derived from the same gene through differential splicing. Intriguingly, CARP also exhibits 64% amino acid sequence identity with the C-terminal part of human doublecortin, encoded by a recently identified gene which is mutated in patients with X-linked lissencephaly and the double-cortex syndrome. In addition, the structure of CARP resembles the autoinhibitory, serine-rich N-terminal domain of CaMK-IV, suggesting a possible modulatory role of CARP with respect to CaMK activity. Northern blot analysis and in situ hybridization experiments showed that CARP mRNA is specifically induced by kainate-elicited seizures in the dentate gyrus and in the pyramidal layers CA1 and CA2, but not in CA3. In contrast, kainate-induced seizures did not change the level of expression of the CaMK-VI gene. We propose that CARP induction leads to the modulation of kinase activity in specific subregions of the rat hippocampus, providing a negative feedback mechanism for seizure-induced kinases.
authors.affiliation: Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Vreugdenhil
authors.forename: N
authors.initials: N
authors.lastname: Datson
authors.forename: B
authors.initials: B
authors.lastname: Engels
authors.forename: J
authors.initials: J
authors.lastname: de Jong
authors.forename: S
authors.initials: S
authors.lastname: van Koningsbruggen
authors.forename: M
authors.initials: M
authors.lastname: Schaaf
authors.forename: E R
authors.initials: ER
authors.lastname: de Kloet
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry; D002352:Carrier Proteins; D003001:Cloning, Molecular; D016384:Consensus Sequence; D018076:DNA, Complementary; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics; D010750:Phosphoproteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D012640:Seizures / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010750:Phosphoproteins; C461219:RNF34 protein, human; D011994:Recombinant Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D007608:Kainic Acid