The Biotechnology Centre of Oslo and Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, P.O. Box 1125, Blindern, N-0317 Oslo, Norway.
Immunol Lett. 2010 Mar 10;129(1):1-6. doi: 10.1016/j.imlet.2010.01.007. Epub 2010 Feb 1.
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 and activation of the cAMP-protein kinase A (PKA)-Csk pathway inhibiting proximal T cell signaling. However, CD28 stimulation leads to recruitment of a beta-arrestin/phosphodiesterase-4 (PDE4) complex to rafts, resulting in down-regulation of cAMP levels. Thus, the activities of both PKA and PDE4 seem to be important for regulation of TCR-induced signaling and T cell function. This review will focus on the novel mechanism whereby CD28 through PI3K regulates recruitment of a PKB/beta-arrestin/PDE4 complex thereby allowing a complete T cell activation to proceed.
T 细胞受体 (TCR) 和 CD28 受体的交联对于完全的 T 细胞激活是必需的。在原发性 T 细胞中 TCR 的交联随后伴随着脂筏中 cAMP 的快速产生和 cAMP-蛋白激酶 A (PKA)-Csk 途径的激活，从而抑制近端 T 细胞信号转导。然而，CD28 刺激导致β-arrestin/磷酸二酯酶-4 (PDE4) 复合物募集到脂筏中，导致 cAMP 水平下调。因此，PKA 和 PDE4 的活性似乎对于 TCR 诱导的信号转导和 T 细胞功能的调节都很重要。这篇综述将重点介绍 CD28 通过 PI3K 调节 PKB/β-arrestin/PDE4 复合物募集的新机制，从而允许完全的 T 细胞激活继续进行。
