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

Citation
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
Citations number
27
Categorie Soggetti
Biology
ISSN journal
00219258
Volume
273
Issue
2
Year of publication
1998
Pages
910 - 916
Database
ISI
SICI code
0021-9258(1998)273:2<910:IRPCET>2.0.ZU;2-1
Abstract
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.