Pka C Beta: A Forgotten Catalytic Subunit Of Camp-Dependent Protein Kinase Opens New Windows For Pka Signaling And Disease Pathologies

3',5'-cyclic adenosine monophosphate (cAMP) dependent protein kinase or protein kinase A (PKA) has served as a prototype for the large family of protein kinases that are crucially important for signal transduction in eukaryotic cells. The PKA catalytic subunits are encoded by the two major genes PRKACA and PRKACB, respectively. The PRKACA gene encodes two known splice variants, the ubiquitously expressed C alpha 1 and the sperm-specifically expressed C alpha 2. In contrast, the PRKACB gene encodes several splice variants expressed in a highly cell and tissue-specific manner. The C beta proteins are called C beta 1, C beta 2, C beta 3, C beta 4 and so-called abc variants of C beta 3 and C beta 4. Whereas C beta 1 is ubiquitously expressed, C beta 2 is enriched in immune cells and the C beta 3, C beta 4 and their abc variants are solely expressed in neuronal cells. All C alpha and C beta splice variants share a kinase-conserved catalytic core and a C-terminal tail encoded by exons 2 through 10 in the PRKACA and PRKACB genes, respectively. All C alpha and C beta splice variants with the exception of C alpha 1 and C beta 1 are hyper-variable at the N-terminus. Here, we will discuss how the PRKACA and PRKACB genes have developed as paralogs that encode distinct and functionally non-redundant proteins. The fact that C alpha and C beta splice variant mutations are associated with numerous diseases further opens new windows for PKA-induced disease pathologies.