S. Orstavik et al., Identification of novel splice variants of the human catalytic subunit c beta of cAMP-dependent protein kinase, EUR J BIOCH, 268(19), 2001, pp. 5066-5073
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.