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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-gamma production in the absence of stimulation via CD3epsilon 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.

Original publication

DOI

10.4049/jimmunol.168.11.5392

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

06/2002

Volume

168

Pages

5392 - 5396

Addresses

Kennedy Institute of Rheumatology Division, Imperial College of Science, Technology, and Medicine, London, United Kingdom. richard.o.williams@ic.ac.uk

Keywords

T-Lymphocytes, CD4-Positive T-Lymphocytes, Animals, Mice, Inbred BALB C, Mice, Cyclic AMP-Dependent Protein Kinases, Carrier Proteins, Cyclic AMP, Cytokines, Lymphocyte Activation