Servicio de Inmunología y Reumatología, Hospital Nacional de Pediatría J. P. Garrahan, Buenos Aires, Argentina.
J Leukoc Biol. 2012 Aug;92(2):301-8. doi: 10.1189/jlb.0212057. Epub 2012 May 17.
This study tested the hypothesis that the IFN-γ R1 287-YVSLI-91 intracellular motif regulates its endocytosis. IFN-γ exerts its biological activities by interacting with a specific cell-surface RC composed of two IFN-γ R1 and two IFN-γ R2 chains. Following IFN-γ binding and along with the initiation of signal transduction, the ligand and IFN-γ R1 are internalized. Two major types of consensus-sorting signals are described in receptors, which are rapidly internalized from the plasma membrane to intracellular compartments: tyrosine-based and dileucine-based internalization motifs. Transfection of HEK 293 cells and IFN-γ R1-deficient fibroblasts with WT and site-directed, mutagenesis-generated mutant IFN-γ R1 expression vectors helped us to identify region IFN-γ R1 287-YVSLI-291 as the critical domain required for IFN-γ-induced IFN-γ R1 internalization and Y287 and LI290-291 as part of a common structure essential for receptor endocytosis and function. This new endocytosis motif, YxxLI, shares characteristics of tyrosine-based and dileucine-based internalization motifs and is highly conserved in IFN-γ Rs across species. The IFN-γ R1 270-LI-271 dileucine motif, previously thought to be involved in this receptor endocytosis, showed to be unnecessary for receptor endocytosis.
这项研究检验了一个假设，即 IFN-γ R1 287-YVSLI-91 细胞内基序调节其内吞作用。IFN-γ 通过与由两个 IFN-γ R1 和两个 IFN-γ R2 链组成的特定细胞表面 RC 相互作用发挥其生物学活性。IFN-γ 结合后，随着信号转导的开始，配体和 IFN-γ R1 被内化。两种主要的受体共识分拣信号被描述为：从质膜快速内化到细胞内隔室的酪氨酸基和双亮氨酸基内化基序。用 WT 和定点突变生成的突变 IFN-γ R1 表达载体转染 HEK 293 细胞和 IFN-γ R1 缺陷型成纤维细胞，帮助我们确定 IFN-γ R1 287-YVSLI-291 区域是 IFN-γ 诱导 IFN-γ R1 内化所必需的关键结构域，而 Y287 和 LI290-291 则是受体内化和功能所必需的共同结构的一部分。这个新的内吞作用基序 YxxLI，具有酪氨酸基和双亮氨酸基内化基序的特征，在跨物种的 IFN-γ Rs 中高度保守。先前认为参与该受体内吞作用的 IFN-γ R1 270-LI-271 二亮氨酸基序，对于受体内吞作用并非必需。
