Cutting edge: A-kinase anchor proteins are involved in maintaining resting T cells in an inactive state.
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.
Williams
Richard O
RO
Kennedy Institute of Rheumatology Division, Imperial College of Science, Technology, and Medicine, London, United Kingdom. richard.o.williams@ic.ac.uk
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology*
D002352:Carrier Proteins; D016207:Cytokines; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases