Developmental regulation of two isoforms of Ca super(2+)/calmodulin-dependent protein kinase I beta in rat brain

Subtractive hybridization analysis of region-specific gene expression in brain has demonstrated a mRNA species enriched in rat hypothalamus [K.M. Gautvik, L. de Lecea, V.T. Gautvik, P.E. Danielson, P. Tranque, A. Dopazo, F.E. Bloom, J.G. Sutcliffe, Proc. Natl. Acad. Sci. USA 93 (1996) 8733-8738.]. We here show that this mRNA encodes a Ca super(2+)/calmodulin-dependent (CaM) kinase belonging in the CaM kinase I beta subgroup. cDNA analysis showed that this enzyme was differentially spliced into two isoforms (designated beta 1 and beta 2) with distinct C-termini. The C-terminal of the translated CaM kinase I beta 2 protein (38.5 kDa molecular size), contained 25 amino acid residues not present in the beta 1 isoform. The two isoforms were differentially developmentally regulated, with the beta 1 isoform being present in rat embryos from day 18 and the beta 2 isoform being present from day 5 postnatally. In situ hybridization analysis of adult rat CNS showed CaM kinase I beta 2 mRNA being enriched in the hypothalamus and the hippocampal formation. Expression was also observed in a number of ventral limbic structures and in the thalamus. Northern blot analysis showed additional expression of multiple beta 2 isoforms in heart and skeletal muscle. The human mRNA showed a similar distribution. Our data suggest that the two isoforms of CaM kinase I beta , created by a splicing process occurring within a week around birth, may have distinct pre- and postnatal functions in a distinct set of CNS neurons and excitable tissues.