Two novel brain-specific splice variants of the murine C beta gene of cAMP-dependent protein kinase

We have previously characterized two murine cAMP-dependent protein kinase catalytic subunit genes, C alpha and C beta 1. Targeted disruption of the C beta 1 promoter revealed two splice variants of the C beta catalytic subunit gene (designated C beta 2 and C beta 3) that continue to be expressed. These variants arise from unique promoters and are brain specific. C beta 2 is expressed in several discrete areas in the limbic system, These include the lateral septum, the bed nucleus of the stria terminalis, the ventral medial hypothalamus, and the amygdala, In the neocortex, expression is highest in cortical areas such as the prefrontal and insular cortex that are associated limbic structures, By contrast, C beta 1 is most highly expressed in the cortex and hippocampus and is also present in all non-neuronal tissues examined, C beta 3 is expressed at very low levels with wide distribution throughout the brain, Both the C beta 2 and C beta 3 variants are enzymatically active and induce gene expression in transient transfections with a cAMP response element-reporter construct, This activity is inhibited by protein kinase A regulatory subunits, the protein kinase inhibitor, and the chemical inhibitor H-89. We also demonstrate that C beta 1 is myristoylated at the amino terminus like the C alpha isoform, but neither C beta 2 nor C beta 3 is myristoylated, The discrete expression of C beta variants in the brain suggests specific functional roles in neuronal signaling.