INSULIN REGULATES PROTEIN-KINASE C-BETA-II EXPRESSION THROUGH ENHANCED EXON INCLUSION IN L6 SKELETAL-MUSCLE CELLS - A NOVEL MECHANISM OF INSULIN-LIKE AND INSULIN-LIKE GROWTH FACTOR-I-INDUCED 5'-SPLICE-SITE SELECTION
Ce. Chalfant et al., INSULIN REGULATES PROTEIN-KINASE C-BETA-II EXPRESSION THROUGH ENHANCED EXON INCLUSION IN L6 SKELETAL-MUSCLE CELLS - A NOVEL MECHANISM OF INSULIN-LIKE AND INSULIN-LIKE GROWTH FACTOR-I-INDUCED 5'-SPLICE-SITE SELECTION, The Journal of biological chemistry, 273(2), 1998, pp. 910-916
The protein kinase C beta (PKC beta) gene encodes two isoforms, PKC be
ta I and PKC beta II, as a result of alternative splicing. The unique
mechanism that underlies insulin-induced alternative splicing of PKC b
eta pre-mRNA was examined in L6 myotubes. Mature PKC beta II mRNA and
protein rapidly increased >3-fold following acute insulin treatment, w
hile PKC beta I mRNA and protein levels remained unchanged. Mature PKC
beta II mRNA resulted from inclusion of the PKC beta II-specific exon
rather than from selection of an alternative polyadenylation site. In
creased PKC beta II expression was also not likely accounted for by tr
anscriptional activation of the gene or increased stabilization of the
PKC beta II mRNA, and suggest that PKC beta II expression is regulate
d primarily at the level of alternative splicing, Insulin effects on e
xon inclusion were observed as early as 15 min after insulin treatment
; by 20 min, a new 5'-splice site variant of PKC beta II was also obse
rved. After 30 min, the longer 5'-splice site variant became the predo
minate species through activation of a downstream 5' splice site, Simi
lar lar results were obtained using IGF-I. Although the role of this n
ew PKC beta II mRNA species is presently unknown, inclusion of either
PKC beta II-specific exon results in the same PKC beta II protein.