Two Novel Brain-specific Splice Variants of the Murine Cβ Gene of cAMP-dependent Protein Kinase*

We have previously characterized two murine cAMP-dependent protein kinase catalytic subunit genes, Cα and Cβ1. Targeted disruption of the Cβ1 promoter revealed two splice variants of the Cβ catalytic subunit gene (designated Cβ2 and Cβ3) that continue to be expressed. These variants arise from unique promoters and are brain-specific. Cβ2 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, Cβ1 is most highly expressed in the cortex and hippocampus and is also present in all non-neuronal tissues examined. Cβ3 is expressed at very low levels with wide distribution throughout the brain. Both the Cβ2 and Cβ3 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 Cβ1 is myristoylated at the amino terminus like the Cα isoform, but neither Cβ2 nor Cβ3 is myristoylated. The discrete expression of Cβ variants in the brain suggests specific functional roles in neuronal signaling.