年間 6 号発行
ISSN 印刷: 1040-8401
ISSN オンライン: 2162-6472
Indexed in
Role of cAMP Phosphodiesterase 4 in Regulation of T-Cell Function
要約
Ligation of both the T-cell receptor (TCR) and the CD28 receptor is required for full T-cell activation to occur. Engagement of the TCR in primary T cells is followed by rapid cAMP production in lipid rafts resulting in raft-associated protein kinase A (PKA) activation and inhibition of proximal T-cell signaling. However, upon TCR and CD28 cross-ligation, β-arrestin in complex with cAMP-specific phosphodiesterase 4 (PDE4) is recruited to lipid rafts, thus downregulating cAMP levels. Consequently, the activities of both PKA and PDE4 seem to be important for the regulation of TCR-induced signaling and T-cell function. We, therefore, propose a novel role for TCR and CD28 co-stimulation in the downmodulation of TCR-induced cAMP-mediated inhibitory signals through the recruitment of β-arrestin and PDE4 to lipid rafts, thus allowing a full T-cell response to occur.
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