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• W1964668822 endingPage "208" @default.
• W1964668822 startingPage "201" @default.
• W1964668822 abstract "We have previously demonstrated that activation of cAMP-dependent protein kinase (cAK) type I (cAKI, RIα2-Cβ2) mediates the inhibitory effects of cAMP on T-cell replication induced through the TCR/CD3 complex. In the present study we have investigated the effect of cAMP on T-cell DNA synthesis, tyrosine phosphorylation of a 100 kDa protein (pp100) and IL2 mRNA expression, induced through stimulation of the TCR/CD3- and/or the CD28 molecules. Our results demonstrate that tyrosine phosphorylation of pp100 stimulated by anti-CD3 is inhibited by cAMP both in the presence and absence of the phorbol ester PMA, and reflects the changes seen in IL2 mRNA expression and T-cell replication. Combined stimulation with anti-CD3 and anti-CD28, which gives a synergistic response in T-cell replication, gave pp100 phosphorylation and IL2 mRNA expression sensitive to cAMP-dependent inhibition. When PMA was added in addition to anli-CD3 and anti-CD28, the inhibitory effect of cAMP on both T-cell replication and pp100 phosphorylation was completely abolished. The fact that pp100 phosphorylation in response to TCR/CD3-, CD28- and PMA stimulation and cAMP mediated inhibition are identical to the effects of the same stimuli on T-cell proliferation, makes this protein an interesting candidate in downstream signalling from these receptors. In addition, our results are compatible with a model where cAMP, through activation of cAKI, eliminates both the PTK and PKC activating capability of the T-cell receptor at a site(s) proximal to PKC activation. Furthermore, the CD28 molecule which activates PTKs, enters the PTK cascade at a point distal to the target(s) for cAKI action. Therefore, during CD28 signalling PKC activation can be achieved either by TCR/CD3 stimulation (inhibited by cAMP), or directly by PMA (not inhibited by cAMP)" @default.
• W1964668822 created "2016-06-24" @default.
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• W1964668822 date "1994-08-01" @default.
• W1964668822 modified "2023-09-25" @default.
• W1964668822 title "Cyclic AMP Sensitive Signalling by the CD28 Marker Requires Concomitant Stimulation by the T-Cell Antigen Receptor (TCR/CD3) Complex" @default.
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• W1964668822 doi "https://doi.org/10.1111/j.1365-3083.1994.tb03451.x" @default.
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