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• W2086421549 startingPage "22648" @default.
• W2086421549 abstract "Insulin regulates the inclusion of the exon encoding protein kinase C (PKC) βII mRNA. In this report, we show that insulin regulates this exon inclusion (alternative splicing) via the phosphatidylinositol 3-kinase (PI 3-kinase) signaling pathway through the phosphorylation state of SRp40, a factor required for insulin-regulated splice site selection for PKCβII mRNA. By taking advantage of a well known inhibitor of PI 3–kinase, LY294002, we demonstrated that pretreatment of L6 myotubes with LY294002 blocked insulin-induced PKCβII exon inclusion as well as phosphorylation of SRp40. In the absence of LY294002, overexpression of SRp40 in L6 cells mimicked insulin-induced exon inclusion. When antisense oligonucleotides targeted to a putative SRp40-binding sequence in the βII-βI intron were transfected into L6 cells, insulin effects on splicing and glucose uptake were blocked. Taken together, these results demonstrate a role for SRp40 in insulin-mediated alternative splicing independent of changes in SRp40 concentration but dependent on serine phosphorylation of SRp40 via a PI 3-kinase signaling pathway. This switch in PKC isozyme expression is important for increases in the glucose transport effect of insulin. Significantly, insulin regulation of PKCβII exon inclusion occurred in the absence of cell growth and differentiation demonstrating that insulin-induced alternative splicing of PKCβII mRNA in L6 cells occurs in response to a metabolic change." @default.
• W2086421549 created "2016-06-24" @default.
• W2086421549 creator A5002759908 @default.
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• W2086421549 creator A5030830595 @default.
• W2086421549 creator A5088862489 @default.
• W2086421549 date "2001-06-01" @default.
• W2086421549 modified "2023-10-13" @default.
• W2086421549 title "Insulin Regulates Alternative Splicing of Protein Kinase C βII through a Phosphatidylinositol 3-Kinase-dependent Pathway Involving the Nuclear Serine/Arginine-rich Splicing Factor, SRp40, in Skeletal Muscle Cells" @default.
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• W2086421549 doi "https://doi.org/10.1074/jbc.m101260200" @default.
• W2086421549 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11283022" @default.
• W2086421549 hasPublicationYear "2001" @default.
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