de Jong R, Loenen W A, Brouwer M, van Emmerik L, de Vries E F, Borst J, van Lier R A
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
J Immunol. 1991 Apr 15;146(8):2488-94.
CD27 belongs to a newly defined family of transmembrane R, including the nerve growth factor R, two distinct TNF R and CD40. The function of CD27 is unknown, but on the basis of structural and functional properties, we postulate that it plays a role in the events subsequent to T cell activation, possibly as a cytokine R. We have analyzed the mechanisms underlying the regulation of CD27 protein expression. Membrane expression of CD27 strongly increases after T cell activation via the TCR/CD3 complex or the CD2 molecule. In contrast, direct stimulation of protein kinase C by phorbol esters markedly down-regulates CD27 surface expression. This down-regulation most likely does not result from CD27 phosphorylation, because both anti-CD3 mAb and PMA induce hyperphosphorylation of CD27 on serine residues. Rather, membrane expression seems to be regulated primarily at the RNA level. Stimulation of T cells with anti-CD3 mAb strongly increases steady state CD27 mRNA levels, whereas PMA treatment greatly reduces these transcript levels. Dissection of the TCR/CD3-induced signaling pathways showed that cytoplasmic cAMP as well as Ca2+ concentrations contribute to the increase of CD27 expression. These data indicate that upon Ag-specific T cell stimulation, membrane expression of CD27 is regulated at the RNA level through the joint action of distinct TCR/CD3-associated signaling pathways.
CD27属于一个新定义的跨膜受体家族，包括神经生长因子受体、两种不同的肿瘤坏死因子受体和CD40。CD27的功能尚不清楚，但基于其结构和功能特性，我们推测它在T细胞活化后的事件中发挥作用，可能作为一种细胞因子受体。我们分析了CD27蛋白表达调控的潜在机制。通过TCR/CD3复合物或CD2分子激活T细胞后，CD27的膜表达显著增加。相反，佛波酯直接刺激蛋白激酶C会明显下调CD27的表面表达。这种下调很可能不是由CD27磷酸化导致的，因为抗CD3单克隆抗体和佛波酯都能诱导CD27丝氨酸残基的过度磷酸化。相反，膜表达似乎主要在RNA水平受到调控。用抗CD3单克隆抗体刺激T细胞会显著增加稳态CD27 mRNA水平，而佛波酯处理则会大大降低这些转录本水平。对TCR/CD3诱导的信号通路进行剖析表明，细胞质中的cAMP以及Ca2+浓度都有助于CD27表达的增加。这些数据表明，在抗原特异性T细胞刺激后，CD27的膜表达通过不同的TCR/CD3相关信号通路的共同作用在RNA水平受到调控。
