Developmental regulation of two isoforms of Ca2+/calmodulin-dependent protein kinase I beta in rat brain

Subtractive hybridization analysis of region-specific gene expression in br ain has demonstrated a mRNA species enriched in rat hypothalamus [K.M. Gaut vik, 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 Ca2+ /calmodulin-dependent (CaM) kinase belonging in the CaM kinase I beta subgroup, cDNA analysis showed that thi s enzyme was differentially spliced into two isoforms (designated beta 1 an d beta 2) with distinct C-termini. The C-terminal of the translated CaM kin ase I beta 2 protein (38.5 kDa molecular size), contained 25 amino acid res idues not present in the pi isoform. The two isoforms were differentially d evelopmentally regulated, with the beta 1 isoform being present in rat embr yos 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. Ex pression was also observed in a number of ventral limbic structures and in the thalamus. Northern blot analysis showed additional expression of multip le beta 2 isoforms in heart and skeletal muscle. The human mRNA showed a si milar distribution. Our data suggest that the two isoforms of CaM kinase I beta, created by a splicing process occurring within a week around birth, m ay have distinct pre- and postnatal functions in a distinct set of CNS neur ons and excitable tissues. (C) 2000 Elsevier Science B.V. All rights reserv ed.