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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白介素 5 (IL-5) 受体 α 链的关键胞质结构域及其在 IL-5 介导的生长信号转导中的功能
DOI：
10.1128/mcb.14.11.7404-7413.1994
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发表时间：
1994
影响因子：
5.3
通讯作者：
Kiyoshi Takatsu
中科院分区：
文献类型：
--
作者：
S. Takaki;Hiroko Kanazawa;Masashi Shiiba;Kiyoshi Takatsu
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和功能。IL-5受体（IL-5 R）由两种不同的膜蛋白α和β组成。α链（IL-5 R α）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）受体的共同β链（β c）。α和β链的胞质结构域对于信号转导是必需的。在这项研究中，我们产生了IL-5 R α的cDNA在其胞质结构域中具有各种突变，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。发现IL-5 R α胞质结构域的膜近端脯氨酸富集序列（在IL-5 R、IL-3R和GM-CSF受体（GM-CSFR）的α链中是保守的）对于IL-5诱导的增殖反应、核原癌基因（如c-jun、c-fos和c-myc）的表达以及细胞蛋白（包括JAK 2蛋白酪氨酸激酶）的酪氨酸磷酸化是必需的。此外，使用由IL-5 R α的细胞外结构域和β c的细胞质结构域组成的嵌合受体的分析表明，β c的细胞质结构域的二聚化可能是激活IL-5 R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 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.
影响因子：
56.9
作者：
REN, RB;MAYER, BJ;BALTIMORE, D
通讯作者：
BALTIMORE, D
影响因子：
56.9
作者：
STAHL, N;BOULTON, TG;YANCOPOULOS, GD
通讯作者：
YANCOPOULOS, GD