Takaki S, Kanazawa H, Shiiba M, Takatsu K
Department of Immunology, University of Tokyo, Japan.
Mol Cell Biol. 1994 Nov;14(11):7404-13. doi: 10.1128/mcb.14.11.7404-7413.1994.
Interleukin-5 (IL-5) regulates the production and function of B cells, eosinophils, and basophils. The IL-5 receptor (IL-5R) consists of two distinct membrane proteins, alpha and beta. The alpha chain (IL-5R alpha) is specific to IL-5. The beta chain is the common beta chain (beta c) of receptors for IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF). The cytoplasmic domains of both alpha and beta chains are essential for signal transduction. In this study, we generated cDNAs of IL-5R alpha having various mutations in their cytoplasmic domains and examined the function of these mutants by expressing them in IL-3-dependent FDC-P1 cells. The membrane-proximal proline-rich sequence of the cytoplasmic domain of IL-5R alpha, which is conserved among the alpha chains of IL-5R, IL-3R, and GM-CSF receptor (GM-CSFR), was found to be essential for the IL-5-induced proliferative response, expression of nuclear proto-oncogenes such as c-jun, c-fos, and c-myc, and tyrosine phosphorylation of cellular proteins including JAK2 protein-tyrosine kinase. In addition, analysis using chimeric receptors which consist of the extracellular domain of IL-5R alpha and the cytoplasmic domain of beta c suggested that dimerization of the cytoplasmic domain of beta c may be an important step in activating the IL-5R complex and transducing intracellular growth signals.
白细胞介素-5（IL-5）调节B细胞、嗜酸性粒细胞和嗜碱性粒细胞的产生及功能。IL-5受体（IL-5R）由两种不同的膜蛋白α链和β链组成。α链（IL-5Rα）对IL-5具有特异性。β链是IL-3和粒细胞-巨噬细胞集落刺激因子（GM-CSF）受体的共用β链（βc）。α链和β链的胞质结构域对于信号转导至关重要。在本研究中，我们构建了胞质结构域存在各种突变的IL-5Rα的cDNA，并通过在依赖IL-3的FDC-P1细胞中表达这些突变体来检测其功能。发现IL-5Rα胞质结构域中靠近膜的富含脯氨酸序列在IL-5R、IL-3R和GM-CSF受体（GM-CSFR）的α链中保守，该序列对于IL-5诱导的增殖反应、核原癌基因如c-jun、c-fos和c-myc的表达以及包括JAK2蛋白酪氨酸激酶在内的细胞蛋白的酪氨酸磷酸化至关重要。此外，使用由IL-5Rα的胞外结构域和βc的胞质结构域组成的嵌合受体进行的分析表明，βc胞质结构域的二聚化可能是激活IL-5R复合物并转导细胞内生长信号的重要步骤。
