Abstract
A profound deficiency of type I protein kinase A (PKA-I or RIalpha/beta2C2) phosphotransferase activity occurs in the T lymphocytes of 80% of subjects with systemic lupus erythematosus (SLE), an autoimmune disorder of unknown etiology. This isozyme deficiency is predominantly the product of reduced or absent beta isoform of the type I regulatory subunit (RIbeta). Transient transfection of RIbeta cDNAs from SLE subjects into autologous T cells that do not synthesize the RIbeta subunit bypassed the block, resulting in RIbeta subunit synthesis and restoration of the PKA-Ibeta (RIbeta2C2) holoenzyme. Transfected T cells activated via the T cell surface receptor complex revealed a significant increase of cAMP-activatable PKA activity that was associated with a significant increase in IL-2 production. These data demonstrate that a disorder of RIbeta translation exists, and that correction of the PKA-I deficiency may enhance T lymphocyte effector functions in SLE.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Cell Line
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Cyclic AMP-Dependent Protein Kinase RIbeta Subunit
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Cyclic AMP-Dependent Protein Kinases / biosynthesis*
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Cyclic AMP-Dependent Protein Kinases / deficiency*
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Cyclic AMP-Dependent Protein Kinases / genetics
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Cyclic AMP-Dependent Protein Kinases / isolation & purification
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Cytomegalovirus / genetics
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Cytomegalovirus / immunology
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DNA, Complementary / biosynthesis
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Enzyme Activation / genetics
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Enzyme Activation / immunology
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Genetic Vectors
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Humans
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Hydrogen-Ion Concentration
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Interleukin-2 / biosynthesis*
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Isoenzymes / biosynthesis
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Isoenzymes / deficiency
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Isoenzymes / genetics
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Isoenzymes / isolation & purification
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Lupus Erythematosus, Systemic / enzymology*
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Lupus Erythematosus, Systemic / genetics
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Lupus Erythematosus, Systemic / immunology*
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Peptide Fragments / biosynthesis
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Peptide Fragments / deficiency
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Peptide Fragments / genetics
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Peptide Fragments / isolation & purification
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Promoter Regions, Genetic / immunology
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Protein Biosynthesis / immunology*
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RNA, Messenger / biosynthesis
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T-Lymphocytes / enzymology*
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T-Lymphocytes / metabolism
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Transfection
Substances
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Cyclic AMP-Dependent Protein Kinase RIbeta Subunit
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DNA, Complementary
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Interleukin-2
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Isoenzymes
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PRKAR1B protein, human
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Peptide Fragments
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RNA, Messenger
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Cyclic AMP-Dependent Protein Kinases