Study of the role of ectokinase on the signal transduction in mast cells

外激酶对肥大细胞信号转导作用的研究

• 批准号: 09672270
• 负责人: TESHIMA Reiko
• 金额: $ 1.79万
• 依托单位: National Institute of Health Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672270/
• 关键词: IgE receptor; Ectokinases; Mast cells; Signal transduction; Degranulation; Calcium signal

We examined the effects of K252b, an ectoprotein kinase inhibitor of microbial origin, on the activation of RBL-2H3 cells by cross-linking of IgB receptors or by the Ca^<2+> ionophore A23187. Analysis of phosphorylation of ectoproteins following IgE receptor cross-linking revealed that K252b mainly inhibited the phosphorylation of a 130-kDa protein. The inhibitor simultaneously inhibited the degranulation and the sustained increase in the cytosolic calcium ion concentration even afteraddition of Ag. In contrast, K252b did not inhibit the increase in degranulation and cytosolic calcium ion concentration caused by stimulation with A23187. Permeation of K252b into RBL-2H3 cells, assessed by fluorescence intensity, was very low. K252b also inhibited de-granulation caused by IgE receptor cross-linking in human basophils, but did not inhibit the de-granuation caused by A23187. Thus, our findings suggest that the effects of K252b may be mediated by outersurface-bound or -anchored K252b-sensitive molecules on RBL-2H3 cells and human basophils, and that the phosphorylation of ectoprotein may be involve a transmembrane influx of Ca^<2+> by IgE rece-ptor cross-linking.

我们检查了微生物起源的蛋白激酶抑制剂K252b对通过IGB受体的交联或通过CA^<2+>离子化体A23187激活RBL-2H3细胞的影响。 IgE受体交联后异损蛋白磷酸化的分析表明，K252B主要抑制130 kDa蛋白的磷酸化。抑制剂同时抑制了即使在Ag的后期，抑制剂也抑制了胞质钙离子浓度的脱粒和持续增加。相比之下，K252b并未抑制由A23187刺激引起的脱粒和胞质钙离子浓度的增加。通过荧光强度评估的K252B渗透到RBL-2H3细胞中非常低。 K252B还抑制了由人类嗜碱性粒细胞IgE受体交联引起的剥离，但并未抑制由A23187引起的颗粒化。 Thus, our findings suggest that the effects of K252b may be mediated by outersurface-bound or -anchored K252b-sensitive molecules on RBL-2H3 cells and human basophils, and that the phosphorylation of ectoprotein may be involve a transmembrane influx of Ca^<2+> by IgE rece-ptor cross-linking.

项目成果

Reiko Teshima: "Effect of an ectokinase inhibitorK252b on degranulatio and Ca^<2+> signals of RBL-2H3 cells and human basophils" J.Immunol.159. 964-969 (1997)

Reiko Teshima：“外激酶抑制剂K252b对RBL-2H3细胞和人嗜碱性粒细胞的脱颗粒和Ca 2+ 信号的影响”J.Immunol.159。

Reiko Teshima: "Effect of ectokinase inhibitor K252b on degranulatio and Ca^<2+> signals of RBL-2H3 cells and human basophils" J.Immunol.159. 964-969 (1997)

Reiko Teshima：“外切激酶抑制剂K252b对RBL-2H3细胞和人嗜碱性粒细胞的脱颗粒和Ca^2信号的影响”J.Immunol.159。

Mayumi Suzuki: "Soluble factors from Rat Basophilic Lenkemia (RBL-2H3) cells stimulated coopera tively the neurite out growth of PC12 cells" Biol.Pharm.Bull.21. 1267-1271 (1998)

Mayumi Suzuki：“来自大鼠嗜碱性粒细胞白血病 (RBL-2H3) 细胞的可溶性因子协同刺激 PC12 细胞的神经突生长”Biol.Pharm.Bull.21。

R.Teshima, Y.Saito, H.Ikebuchi, N.R.D.Silva, Y.Morita, M.Nakanishi, J.Sawada and S.Kitani: "Effect of an ecto-kinase inhibitor, K252b, on degranulation and Ca2+ signals of RBL-2H3 cells and human basophils" J.Immunology. 159. 964 (1997)

R.Teshima、Y.Saito、H.Ikebuchi、N.R.D.Silva、Y.Morita、M.Nakanishi、J.Sawada 和 S.Kitani：“外激酶抑制剂 K252b 对 RBL- 脱颗粒和 Ca2 信号的影响

M.Nakanishi and R.Teshima: "Cell signaling and imaging in mast cell activation" Current Trends in Immunol.(in press). (1999)

M.Nakanishi 和 R.Teshima：“肥大细胞激活中的细胞信号传导和成像”免疫学当前趋势（正在出版）。