Involvement of farnesyl protein transferase (FPTase) in FcarepsilonRI-induced activation of RBL-2H3 mast cells.
Involvement of farnesyl protein transferase (FPTase) in FcarepsilonRI-induced activation of RBL-2H3 mast cells.
复制标题
法尼基蛋白转移酶 (FPTase) 参与 FcarepsilonRI 诱导的 RBL-2H3 肥大细胞激活。
DOI：
10.1006/abbi.1999.1131
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发表时间：
1999
影响因子：
3.9
通讯作者：
Shechter,I
中科院分区：
文献类型：
--
作者：
Chen,HT;Mehan,RS;Gupta,SD;Goldberg,I;Shechter,I
在 IgE 致敏的 RBL-2H3 肥大细胞中测定法呢基蛋白转移酶 (FPTase) 活性和 FPTase β 亚基蛋白水平的变化，以响应多价抗原的施用。向肥大细胞添加 DNP 修饰的 BSA 十分钟后，肥大细胞的 IgE 高亲和力受体 (FcεRI) 含有结合的抗 DNP IgE，FPTase 比活性增加 54 ± 28%。时程研究表明，FPTase 比活性在抗原诱导的细胞聚集后 20 至 30 分钟内翻倍。此外，在此期间观察到 FPTase β 亚基蛋白增加 (∼30%)；这种蛋白质的增加并不伴随着 FPTase β-亚基 mRNA 水平的类似增加。 FcεRI 聚集对参与法呢基二磷酸 (FPP) 代谢的其他酶的活性没有显着影响：FPP 合酶、异戊烯基二磷酸异构酶、香叶基香叶基蛋白转移酶和角鲨烯合酶。研究了手霉素对 FPTase 活性的特异性抑制，以确定 FPTase 在肥大细胞活化中发挥的作用。 Manumycin 深度抑制活化细胞中氨基己糖苷酶的释放，表明 FPTase 是参与 RBL-2H3 肥大细胞蛋白胞吐作用的信号转导所必需的。
Changes in farnesyl protein transferase (FPTase) activity and FPTase β-subunit protein levels were determined in IgE-sensitized RBL-2H3 mast cells in response to polyvalent antigen administration. Ten minutes after the addition of DNP modified BSA to mast cells, whose high affinity receptor for IgE (FcεRI) contained bound anti-DNP IgE, FPTase specific activity increased by 54 ± 28%. Time course studies showed FPTase specific activity doubled during a 20- to 30-min period after antigen-induced cell aggregation. Also, an increase in FPTase β-subunit protein during this time (∼30%) was observed; this protein increase was not accompanied by a similar increase in FPTase β-subunit m-RNA levels. The FcεRI aggregation had no significant effect on the activities of other enzymes involved with farnesyl diphosphate (FPP) metabolism: FPP synthase, isopentenyl diphosphate isomerase, geranylgeranyl protein transferase, and squalene synthase. Specific inhibition of FPTase activity by manumycin was studied to determine what role FPTase plays in mast cell activation. Manumycin profoundly inhibited hexosaminidase release in activated cells, indicating FPTase is required for signal transduction involved with protein exocytosis from RBL-2H3 mast cells.