Bader T, Wietzerbin J
Institut Curie, Unité 365 INSERM, Paris, France.
Cytokine. 1994 Jan;6(1):70-8. doi: 10.1016/1043-4666(94)90010-8.
IFN-gamma receptor expression on murine leukaemic L1210-cells has been studied. With the help of a transfected cell-line expressing the heterologous human receptor it was possible to discern receptor-specific properties like internalization from those regulating their expression on the surface. Recombinant IFN-gamma binds specifically to its homologous receptor at 4 degrees C and is rapidly internalized at physiologic temperatures. For this effect to occur, ligand binding to its receptor at 37 degrees C is necessary and sufficient. This notion is confirmed since a reduction in the number of heterologous human IFN-gamma receptors on the murine cell surface occurred exclusively after treatment with human IFN-gamma. Even weak doses of ligand, insufficient to occupy all receptors, led to a pronounced disappearance of binding sites. However, both receptors are simultaneously up-regulated in the presence of TPA, indicating a separate pathway which is not species-specific. Our findings imply that similar elements of the intracellular signal transduction machinery are involved in the control of MuIFN-gamma and HuIFN-gamma receptor expression. The results indicate also that factors involved in binding, internalization, and regulation of receptor gene expression are not species-specific.
对小鼠白血病L1210细胞上的γ干扰素受体表达进行了研究。借助表达异源人类受体的转染细胞系,能够区分受体特异性特性,如内化作用与调节其表面表达的特性。重组γ干扰素在4℃时特异性结合其同源受体,并在生理温度下迅速内化。要产生这种效应,配体在37℃时与受体结合是必要且充分的。这一观点得到了证实,因为仅在用人类γ干扰素处理后,小鼠细胞表面异源人类γ干扰素受体的数量才会减少。即使是不足以占据所有受体的低剂量配体,也会导致结合位点明显消失。然而,在佛波酯(TPA)存在的情况下,两种受体同时上调,表明存在一条不具有物种特异性的独立途径。我们的研究结果表明,细胞内信号转导机制的类似元件参与了对小鼠γ干扰素和人类γ干扰素受体表达的控制。结果还表明,参与受体结合、内化和基因表达调节的因子不具有物种特异性。