CD3- and CD28-dependent induction of PDE7 required for T cell activation |
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Authors: | L Li C Yee JA Beavo |
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Affiliation: | Department of Pharmacology and Molecular and Cellular Biology Program, Box 357280, University of Washington School of Medicine, Seattle, WA 98195, USA. |
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Abstract: | Costimulation of both the CD3 and CD28 receptors is essential for T cell activation. Induction of adenosine 3',5'-monophosphate (cAMP)-specific phosphodiesterase-7 (PDE7) was found to be a consequence of such costimulation. Increased PDE7 in T cells correlated with decreased cAMP, increased interleukin-2 expression, and increased proliferation. Selectively reducing PDE7 expression with a PDE7 antisense oligonucleotide inhibited T cell proliferation; inhibition was reversed by blocking the cAMP signaling pathways that operate through cAMP-dependent protein kinase (PKA). Thus, PDE7 induction and consequent suppression of PKA activity is required for T cell activation, and inhibition of PDE7 could be an approach to treating T cell-dependent disorders. |
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