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• W4313333693 startingPage "5639" @default.
• W4313333693 abstract "Abstract Deficient type I protein kinase A phosphotransferase activity occurs in the T cells of 80% of subjects with systemic lupus erythematosus (SLE). To investigate the mechanism of this deficient isozyme activity, we hypothesized that reduced amounts of type I regulatory (RI) isoform transcripts, RIα and RIβ, may be associated with a diminution of RIα and/or RIβ protein. Sixteen SLE subjects with a mean (±1 SD) SLE disease activity index of 12.4 ± 7.2 were studied. Controls included 16 normal subjects, six subjects with primary Sjögren’s syndrome (SS), and three subjects with SS/SLE overlap. RT-PCR revealed that normal, SS, SS/SLE, and SLE T cells expressed mRNAs for all seven R and catalytic (C) subunit isoforms. Quantification of mRNAs by competitive PCR revealed that the ratio of RIα mRNA to RIβ mRNA in normal T cells was 3.4:1. In SLE T cells there were 20 and 49% decreases in RIα and RIβ mRNAs (RIβ; p = 0.008), respectively, resulting in an RIα:RIβ mRNA of 5.3:1. SS/SLE T cells showed a 72.5% decrease in RIβ mRNA compared with normal controls (p = 0.01). Immunoblotting of normal T cell RIα and RIβ proteins revealed a ratio of RIα:RIβ of 3.2:1. In SLE T cells, there was a 30% decrease in RIα protein (p = 0.002) and a 65% decrease in RIβ protein (p &lt; 0.001), shifting the ratio of RIα:RIβ protein to 6.5:1. T cells from 25% of SLE subjects lacked any detectable RIβ protein. Analysis of several lupus T cell lines demonstrated a persistent deficiency of both proteins, excluding a potential effect of disease activity. In conclusion, reduced expression of RIα and RIβ transcripts is associated with a decrement in RIα and RIβ proteins and may contribute to deficient type I protein kinase A isozyme activity in SLE T cells." @default.
• W4313333693 created "2023-01-06" @default.
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• W4313333693 date "1999-05-01" @default.
• W4313333693 modified "2023-10-06" @default.
• W4313333693 title "Diminished Levels of Protein Kinase A RIα and RIβ Transcripts and Proteins in Systemic Lupus Erythematosus T Lymphocytes" @default.
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• W4313333693 doi "https://doi.org/10.4049/jimmunol.162.9.5639" @default.
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