1993年12月
INHIBITION OF HISTAMINE-SECRETION BY WORTMANNIN THROUGH THE BLOCKADE OF PHOSPHATIDYLINOSITOL 3-KINASE IN RBL-2H3 CELLS
JOURNAL OF BIOLOGICAL CHEMISTRY
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- 巻
- 268
- 号
- 34
- 開始ページ
- 25846
- 終了ページ
- 25856
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- 出版者・発行元
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
The surface engagement of high affinity immunoglobulin E receptor (FcepsilonRI) of rat basophilic leukemia 2H3 (RBL-2H3) cells induced histamine secretion and leukotriene release following activation of the tyrosine kinase Lyn together with phosphatidylinositol 3-kinase (PI3-kinase). Wortmannin inhibited the activity of partially purified PI3-kinase from calf thymus, as well as the PI3-kinase activity in anti-PI3-kinase p85 immunoprecipitates from RBL-2H3 cells, at a concentration as low as 1.0 nM and with IC50 values of 3.0 nM, but did not inhibit P14-kinase activity. The inhibition of PI3-kinase by wortmannin was irreversible. Wortmannin inhibited both FcepsilonRI-mediated histamine secretion and leukotriene release up to 80% with IC50 values of 2.0 and 3.0 nM, respectively. Wortmannin inhibited PI3-kinase activity in intact cells up to 80% with an IC50 value of 2.0 nM, which is almost equal to those for PI3-kinase in vitro and for histamine secretion and leukotriene release. With anti-wortmannin antibody, we have shown that wortmannin binds to the 110-kDa protein, but not to P13-kinase 85-kDa regulatory subunit both in vitro and in whole cells. Furthermore, there was a positive correlation between the potencies of wortmannin derivatives as inhibitors of P13-kinase and as inhibitors of histamine secretion. Wortmannin had no effect on the activation of the tyrosine kinase Lyn. These results suggest that P13-kinase is involved in the signal transduction pathway responsible for histamine secretion following stimulation of FcepsilonRI and that wortmannin blocks these responses through direct interaction with the catalytic subunit of this enzyme.
- リンク情報
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- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:A1993MK10000082&DestApp=WOS_CPL
- URL
- http://www.scopus.com/inward/record.url?eid=2-s2.0-0027374488&partnerID=MN8TOARS
- URL
- http://orcid.org/0000-0002-3359-1578
- ID情報
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- ISSN : 0021-9258
- ORCIDのPut Code : 20897396
- SCOPUS ID : 0027374488
- Web of Science ID : WOS:A1993MK10000082