Identification of novel splice variants of the human catalytic subunit c beta of cAMP-dependent protein kinase

Four different isoforms of the catalytic subunit of cAMP-dependent protein kinase, termed C alpha, C beta, C gamma and PrKX have been identified. Here we demonstrate that the human C beta gene encodes six splice variants, des ignated C beta1, C beta2, C beta3, C beta4, C beta 4ab and C beta 4abc. The C beta splice variants differ in their N-terminal ends due to differential splicing of four different forms of exon 1 designated exon 1-1, 1-2, 1-3, 1-4 and three exons designated a, b and c. All these exons are located upst ream of exon 2 in the C beta gene. The previously identified human C beta v ariant has been termed C beta1, and is similar to the C beta isoform identi fied in the mouse, ox, pig and several other mammals. Human C beta2, which is the homologue of bovine C beta2, has no homologue in the mouse. Human C beta3 and C beta4 are homologous to the murine C beta3 and C beta2 splice v ariants, whereas human C beta 4ab and C beta 4abc represent novel isofoms p reviously not identified in any other species. At the mRNA level, the C bet a splice variants reveal tissue specific expression. C beta1 was most abund antly expressed in the brain, with low-level expression in several other ti ssues. The C beta3 and C beta4 splice variants were uniquely expressed in h uman brain in contrast to C beta2, which was most abundantly expressed in t issues of the immune system, with no detectable expression in brain. We sug gest that the various C beta splice variants when complexed with regulatory subunits may give rise to novel holoenzymes of protein kinase A that may b e important for mediating specific effects of cAMP.