Modulation of murine and human interferon-gamma receptor expression by their ligands or phorbol ester.
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.
Bader
T
T
Institut Curie, Unité 365 INSERM, Paris, France.
Wietzerbin
J
J
D000818:Animals; D015152:Blotting, Northern; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D007939:Leukemia L1210 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D017471:Receptors, Interferon / Q000096:biosynthesis* / Q000378:metabolism; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate; D000096743:Interferon gamma Receptor