Hou J, Schindler U, Henzel W J, Ho T C, Brasseur M, McKnight S L
Tularik, Inc., South San Francisco, CA 94080.
Science. 1994 Sep 16;265(5179):1701-6. doi: 10.1126/science.8085155.
Interleukin-4 (IL-4) is an immunomodulatory cytokine secreted by activated T lymphocytes, basophils, and mast cells. It plays an important role in modulating the balance of T helper (Th) cell subsets, favoring expansion of the Th2 lineage relative to Th1. Imbalance of these T lymphocyte subsets has been implicated in immunological diseases including allergy, inflammation, and autoimmune disease. IL-4 may mediate its biological effects, at least in part, by activating a tyrosine-phosphorylated DNA binding protein. This protein has now been purified and its encoding gene cloned. Examination of the primary amino acid sequence of this protein indicates that it is a member of the signal transducers and activators of transcription (Stat) family of DNA binding proteins, hereby designated IL-4 Stat. Study of the inhibitory activities of phosphotyrosine-containing peptides derived from the intracellular domain of the IL-4 receptor provided evidence for direct coupling of receptor and transcription factor during the IL-4 Stat activation cycle. Such observations indicate that IL-4 Stat has the same functional domain for both receptor coupling and dimerization.
白细胞介素-4（IL-4）是一种由活化的T淋巴细胞、嗜碱性粒细胞和肥大细胞分泌的免疫调节细胞因子。它在调节辅助性T（Th）细胞亚群的平衡中起重要作用，相对于Th1细胞，它更有利于Th2细胞系的扩增。这些T淋巴细胞亚群的失衡与包括过敏、炎症和自身免疫性疾病在内的免疫疾病有关。IL-4可能至少部分地通过激活一种酪氨酸磷酸化的DNA结合蛋白来介导其生物学效应。这种蛋白现已被纯化，其编码基因也已被克隆。对该蛋白一级氨基酸序列的研究表明，它是DNA结合蛋白信号转导和转录激活因子（Stat）家族的成员，因此被命名为IL-4 Stat。对源自IL-4受体胞内结构域的含磷酸酪氨酸肽的抑制活性研究，为IL-4 Stat激活周期中受体与转录因子的直接偶联提供了证据。这些观察结果表明，IL-4 Stat在受体偶联和二聚化方面具有相同的功能结构域。
