A CRITICAL CYTOPLASMIC DOMAIN OF THE INTERLEUKIN-5 (IL-5) RECEPTOR-ALPHA CHAIN AND ITS FUNCTION IN IL-5-MEDIATED GROWTH SIGNAL-TRANSDUCTION
A CRITICAL CYTOPLASMIC DOMAIN OF THE INTERLEUKIN-5 (IL-5) RECEPTOR-ALPHA CHAIN AND ITS FUNCTION IN IL-5-MEDIATED GROWTH SIGNAL-TRANSDUCTION
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DOI：
10.1128/mcb.14.11.7404
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发表时间：
1994-11-01
影响因子：
5.3
通讯作者：
TAKATSU, K
中科院分区：
文献类型：
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作者：
TAKAKI, S;KANAZAWA, H;TAKATSU, K
白介素 5 (IL-5) 调节 B 细胞、嗜酸性粒细胞和嗜碱性粒细胞的产生和功能。 IL-5 受体 (IL-5R) 由两种不同的膜蛋白 α 和 β 组成。 α链 (IL-5R α) 是 IL-5 的特异性。 β 链是 IL-3 和粒细胞巨噬细胞集落刺激因子 (GM-CSF) 受体的共同 β 链 (β c)。 α链和β链的细胞质结构域对于信号转导都是必需的。在这项研究中，我们生成了在细胞质结构域中具有各种突变的 IL-5R α cDNA，并通过在 IL-3 依赖性 FDC-P1 细胞中表达它们来检查这些突变体的功能。 IL-5R α 胞质结构域的近膜富含脯氨酸的序列在 IL-5R、IL-3R 和 GM-CSF 受体 (GM-CSFR) 的链中保守，被发现对于 ICS 诱导的增殖反应、核原癌基因（如 c-jun、c-fos 和 c-myc）的表达以及细胞蛋白的酪氨酸磷酸化至关重要，其中包括JAK2 蛋白酪氨酸激酶。此外，使用由IL-5Rα的胞外结构域和pc的胞质结构域组成的嵌合受体进行的分析表明，βc的胞质结构域的二聚化可能是激活IL-5R复合物和转导细胞内生长信号的重要步骤。
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 or chains of IL-5R, IL-3R, and GM-CSF receptor (GM-CSFR), was found to be essential for the ICS-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 pc 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.