Characterization of receptors for human colony-stimulating factor (GM-CSF and IL-3)

人集落刺激因子（GM-CSF 和 IL-3）受体的表征

• 批准号: 01570675
• 负责人: MIYAGAWA Kiyoshi
• 金额: $ 1.47万
• 依托单位: Tokyo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570675/
• 关键词: colony-stimulating factor; IL-3; GM-CSF; soluble receptor; 分泌型受容体; 造血因子; インタ-ロイキン3; 受容体; GM-CSF

GM-CSF and EL-3 can act on a broad range of hematopoietic cells and support their growth and differentiation. Although their biological role is striking, little is known about the molecular mechanism of their intracellular signaling pathway. In this study, we have demonstrated that high affinity-binding site of GM-CSF is partially blocked by the addition of IL-3.We have also shown that low affinity receptor for GM-CSF is expressed not only in hematopoietic cells but also in a human choriocarcinoma line. Furthen-nore, addition of GM-CSF to this cell line could induce the production of gonadotropin. Therefore, 1E is likely that low affinity receptor for GM-CSF itself can transduce some signals.Recently, soluble type of receptors has been identified for many lymphokines. These soluble receptors are presumed to have significant biological role, such as competitive inhibitor of membrane receptor. We. could reveal that there is a soluble type of GMCSF receptor. A soluble protein of 62 kDa in the supernatant of a human choriocarcinoma cell line was shown to bind to ^<125>I-labeled GM-CSF. This binding was specifically blocked by the excess addition of non-labeled GM-CSF. We could not recognize this type of receptor in the supernatant of hematopoietic cells.The structure and the biological role of this soluble GM-CSF receptor is currently under investigation.

GM-CSF和EL-3可以作用于广泛的造血细胞并支持其生长和分化。虽然它们的生物学作用是惊人的，但对其细胞内信号通路的分子机制知之甚少。本研究证实，IL-3可部分阻断GM-CSF的高亲和力结合位点，并发现GM-CSF的低亲和力受体不仅在造血细胞中表达，而且在人绒毛膜癌细胞系中也有表达。此外，GM-CSF还能诱导该细胞产生促性腺激素。因此，1 E可能是GM-CSF的低亲和力受体本身就能阻断某些信号。这些可溶性受体被认为具有重要的生物学作用，如膜受体的竞争性抑制剂。We.可以揭示存在一种可溶性的GM-CSF受体。人绒毛膜癌细胞系上清液中的62 kDa可溶性蛋白质显示与13 <125>I标记的GM-CSF结合。这种结合被过量添加的未标记的GM-CSF特异性阻断。在造血细胞培养上清中不能识别这种受体，其结构和生物学作用尚在进一步研究中。

项目成果

Taketazu,F.: "IL-3 specifically inhibits GM-CSF binding to thehigher affinity receptor." J.Cell.Physiol.146. 251-257 (1991)

Taketazu, F.：“IL-3 特异性抑制 GM-CSF 与更高亲和力受体的结合。”

K.Shibuya,S.Chiba,K.Miyazono,F.Takaku,et al.: "Effects of ubenimex on proliferation and differentiation of human bone marrow cells and leukemic cell lines,and the possible mechanisms of its action." Experimental Hematology Today. (1990)

K.Shibuya,S.Chiba,K.Miyazono,F.Takaku,et al.：“乌苯美克斯对人骨髓细胞和白血病细胞系增殖和分化的影响及其可能的作用机制。”

Hirai,H.: "Analysis of Ph1ーpositive leukemia by PCR" Jpn.Clinical Hematol.32. 319-326 (1991)

Hirai, H.：“Ph1 阳性白血病的 PCR 分析”Jpn.Clinical Hematol.32（1991）。

Hirai,H.: "Analysis of Ph1-positive leukemia by PCR." Jpn.Clinical Hematol.32. 319-326 (1991)

Hirai,H.：“通过 PCR 分析 Ph1 阳性白血病。”

Tanaka, T., Suda, T., Suda, J., Inoue, T., Hirabayashi, Y., Hirai, H., Takaku, F., Miura, Y.: "Stimulatory effects of granulocyte colony -stimulating factor on CFU-S differentiation and pre-CFU-S proliferation in mice." Blood. 77. 2597-2602 (1991)

Tanaka, T.、Suda, T.、Suda, J.、Inoue, T.、Hirabayashi, Y.、Hirai, H.、Takaku, F.、Miura, Y.：“粒细胞集落刺激因子对