Signaling through surface receptors in immune cells.
通过免疫细胞表面受体发出信号。
基本信息
- 批准号:09044263
- 负责人:
- 金额:$ 3.46万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for international Scientific Research
- 财政年份:1997
- 资助国家:日本
- 起止时间:1997 至 1998
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The human IL-5R (hIL-5R) consists of two distinct polypeptide chains, alpha and beta which activates JAK1 and JAK2 and STAT5. We analyzed the interaction between hIL-5Ralpha and betac by immuno-precipitation using anti-hIL-5Ralpha and anti-betac mAbs. The binding of JAK1 and JAK2 to each hIL-5R subunit was also evaluated inTF-h5Ralpha. IL-5 stimulation induced the recruitment of betac to hIL-5Ralpha, although in the absence of IL-5 the subunits remained independent. JAK2 and JAK1 were associated with hIL-5Ralpha and betac, respectively. IL-S stimulation resulted in tyrosine phosphoryl-ation of JAK2, JAK1, betac, and STAT5. Moreover, IL-5-induced dimerization of IL-5R subunits caused JAK2 activation and the betac phosphorylation. Furthermore, tyrosine phosphorylation of JAK1 depended on the activation of JAK2. The cytoplasmic stretch at position 346-387, containing the proline-rich region was necessary for JAK2 binding. These observations suggest that activation of hIL-5Ralpha associated JAK2 is indispensable for IL-5 signaling event.Bone-marrow derived mast cells adhered to fibronectin via VLA-5 (alpha5beta1) upon stimulation with steel factor (SLF) and FceRI cross-linking as well as PMA.SLF and PMA, but not FcepsilonRI cross-linking induced a diffusion of VLA-5 as well as drastic morphological changes. In contrast, only FcepsilonRI cross-linking increased affinity of VLA-5. We also showed PI 3-kinase as a critical affinity modulator by a specific inhibitor, wortmannin, and by introduction ofa constitutively active p110 subunit ofPI-3 kinase. Utilization of affinity or spatial modulation of VLA-5 caused differential effects on adhesion in the presence of physiological concentrations of soluble fibronectin. Our findings indicate that adhesion via VLA-5 are regulated physiologically by two mechanisms ; affinity modulation through PI 3-kinase and spatial modulation possibly through protein kinase C.
人IL-5 R(hIL-5 R)由两条不同的多肽链α和β组成,其激活JAK 1和JAK 2以及STAT 5。我们通过使用抗hIL-5 R α和抗betac mAb的免疫沉淀分析了hIL-5 R α和betac之间的相互作用。JAK 1和JAK 2与每个hIL-5 R亚基的结合也在TF-h5 R α中评估。IL-5刺激诱导betac向hIL-5 R α的募集,尽管在不存在IL-5的情况下,亚基保持独立。JAK 2和JAK 1分别与hIL-5 R α和betac相关。IL-S刺激导致JAK 2、JAK 1、betac和STAT 5的酪氨酸磷酸化。此外,IL-5诱导的IL-5 R亚基的二聚化引起JAK 2活化和betac磷酸化。此外,JAK 1的酪氨酸磷酸化依赖于JAK 2的激活。在位置346-387处的细胞质伸展,含有富含脯氨酸的区域是JAK 2结合所必需的。结果表明,hIL-5 R α相关的JAK 2的激活是IL-5信号转导过程中不可或缺的一个环节,骨髓来源的肥大细胞在钢因子(SLF)和FceRI交联以及PMA的刺激下,通过VLA-5(α 5 β 1)粘附于纤维连接蛋白,SLF和PMA可诱导VLA-5的扩散,而FceplonRI交联则不能诱导VLA-5的扩散以及细胞形态学的显著变化。相比之下,仅Fc ε RI交联增加VLA-5的亲和力。我们还表明PI 3激酶作为一个关键的亲和力调节剂的特异性抑制剂,渥曼青霉素,并通过引入一个组成型活性p110亚基的PI 3激酶。在生理浓度的可溶性纤连蛋白存在下,利用VLA-5的亲和力或空间调制对粘附产生不同的影响。我们的研究结果表明,通过VLA-5的粘附在生理上受到两种机制的调节:通过PI 3-激酶的亲和力调节和可能通过蛋白激酶C的空间调节。
项目成果
期刊论文数量(27)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
K.Takatsu, et al.: "Suppression of autoimmune disease and of massive lymphadenopathy in MRL/MP-lpr/lpr mice lacking tyrosine kinase fyn (p59fyn)." J. Immunol.159. 2532-2541 (1997)
K.Takatsu 等人:“在缺乏酪氨酸激酶 fyn (p59fyn) 的 MRL/MP-lpr/lpr 小鼠中抑制自身免疫性疾病和大量淋巴结病。”
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
K.Takatsu. et al.: "JAK2 and JAK1 are constitutively associate with an interleukin-5 (IL-5) receptor α and βc subunit, respectively, and are activated upon IL-5 stimulation." Blood. 91. 2264-2271 (1998)
K.Takatsu. 等人:“JAK2 和 JAK1 分别与白细胞介素 5 (IL-5) 受体 α 和 βc 亚基相关,并在 IL-5 刺激下被激活。” 2264-2271 血液。 (1998)
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- 影响因子:0
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- 通讯作者:
Hirota, J., M.Baba, M.Matsumoto, K.Takatsu, et al.: "T-cell-receptor signaling in inositol 1,4,5-triphosphate receptor (IP3R) type-1-deficient mice : is IP3R type 1 ssential for T-cell-receptor signaling?" Biochem.J.333. 615-619 (1998)
Hirota, J.、M.Baba、M.Matsumoto、K.Takatsu 等人:“肌醇 1,4,5-三磷酸受体 (IP3R) 1 型缺陷小鼠中的 T 细胞受体信号传导:是 IP3R
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- 影响因子:0
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Yasue, T., Baba, M., S.Mori, K.Takatsu, et al.: "IgG1 production by sIgD+splenic B cells and peritoneal B-1 cells in response to IL-5 and CD38 ligation." Int.Immunol.in press. (1999)
Yasue, T.、Baba, M.、S.Mori、K.Takatsu 等人:“sIgD 脾 B 细胞和腹膜 B-1 细胞响应 IL-5 和 CD38 连接而产生 IgG1。”
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- 影响因子:0
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Ogata N. et al.: "An interleulin 5 (IL-5) receptor α subunit provides a binding site for IL-5 and functional signaling molecules as well." Blood, in press,. (1997)
Ogata N. 等人:“白介素 5 (IL-5) 受体 α 亚基也提供了 IL-5 和功能性信号分子的结合位点,正在出版。”
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- 影响因子:0
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TAKATSU Kiyoshi其他文献
TAKATSU Kiyoshi的其他文献
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{{ truncateString('TAKATSU Kiyoshi', 18)}}的其他基金
Analysis of innate IL-5 producing cells in immune responses and chronic inflammation
免疫反应和慢性炎症中先天性 IL-5 产生细胞的分析
- 批准号:
24390119 - 财政年份:2012
- 资助金额:
$ 3.46万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Spatiotemporal control of allergy and non-infectious inflammation and their regulation by natural products
过敏和非感染性炎症的时空控制及其天然产物的调节
- 批准号:
23659247 - 财政年份:2011
- 资助金额:
$ 3.46万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Roles of cytokines and TLRs in lymphocyte activation and differentiation
细胞因子和 TLR 在淋巴细胞活化和分化中的作用
- 批准号:
20390141 - 财政年份:2008
- 资助金额:
$ 3.46万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Enhancement of Th1 and antitumor immunity by Ag85B and Peptide-25.
Ag85B 和 Peptide-25 增强 Th1 和抗肿瘤免疫力。
- 批准号:
17013024 - 财政年份:2005
- 资助金额:
$ 3.46万 - 项目类别:
Grant-in-Aid for Scientific Research on Priority Areas
Investigation of regulatory mechanisms for homeostasis and activation of lymphocyte
淋巴细胞稳态和激活调节机制的研究
- 批准号:
16109004 - 财政年份:2004
- 资助金额:
$ 3.46万 - 项目类别:
Grant-in-Aid for Scientific Research (S)
REGULATORY MECHANISMS OF IL-5 DEPENDENT IMMUNE REGULATION
IL-5依赖性免疫调节的调节机制
- 批准号:
13307012 - 财政年份:2001
- 资助金额:
$ 3.46万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Molecular mechanisms of isotype switch recombination.
同型转换重组的分子机制。
- 批准号:
11470083 - 财政年份:1999
- 资助金额:
$ 3.46万 - 项目类别:
Grant-in-Aid for Scientific Research (B).
Molecular mechanisms of oral immunity : Role of IL-5 in potentiation of IgA production in mucosal lymphoid cell
口腔免疫的分子机制:IL-5 在增强粘膜淋巴细胞 IgA 产生中的作用
- 批准号:
10557036 - 财政年份:1998
- 资助金额:
$ 3.46万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Molecular mechanisms of proliferation and differentiation of germinal center B cells
生发中心B细胞增殖分化的分子机制
- 批准号:
09470091 - 财政年份:1997
- 资助金额:
$ 3.46万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Molecular Mechanisms and Intervention of Immunological Diseases.
免疫疾病的分子机制和干预。
- 批准号:
08282101 - 财政年份:1996
- 资助金额:
$ 3.46万 - 项目类别:
Grant-in-Aid for Scientific Research on Priority Areas
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