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Cutting Edge |
Kennedy Institute of Rheumatology Division, Imperial College of Science, Technology, and Medicine, London, United Kingdom
A-kinase anchor proteins (AKAPs) target protein kinase A (PKA)
to different subcellular locations and are thought to play important
roles in the cAMP signaling pathway. The aims of this study were to
determine whether T cells express AKAPs and, if so, to establish their
physiological significance. CD4+ T cells were found to
express eight AKAPs. Disruption of the AKAP-PKA interaction caused high
levels of IL-2, IL-4, IL-5, and IFN-
production in the absence of
stimulation via CD3
and CD28 molecules. Disruption of the AKAP-PKA
interaction acted synergistically with suboptimal doses of Ag in
boosting proliferative responses of T cells. Finally, disruption of the
AKAP-PKA interaction rendered T cells insensitive to cAMP-elevating
agents. It was concluded that AKAPs, through their association with
PKA, are involved in maintaining T cell homeostasis and in regulating
the sensitivity of T cells to incoming cAMP
signals.
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