PI3K and Btk differentially regulate B cell antigen receptor-mediated signal transduction

被引：118

作者：

Suzuki, H

Matsuda, S

Terauchi, Y

Fujiwara, M

Ohteki, T

Asano, T

Behrens, TW

Kouro, T

Takatsu, K

Kadowaki, T

Koyasu, S ^{[1
]}

机构：

[1] Keio Univ, Sch Med, Dept Microbiol & Immunol, Tokyo 1608582, Japan

[2] Japan Sci & Technol Corp, CREST, Kawaguchi 3320012, Japan

[3] Univ Tokyo, Grad Sch Med, Dept Metab Dis, Tokyo 1138655, Japan

[4] Univ Minnesota, Ctr Immunol, Dept Med, Minneapolis, MN 55455 USA

[5] Univ Tokyo, Inst Med Sci, Dept Immunol, Tokyo 1088639, Japan

来源：

NATURE IMMUNOLOGY | 2003年 / 4卷 / 03期

基金：

日本学术振兴会;

关键词：

D O I：

10.1038/ni890

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Phosphoinositide-3 kinase (PI3K) is thought to activate the tyrosine kinase Btk. However, through analysis of PI3K(-/-) and Btk(-/-) mice, B cell antigen receptor (BCR)-induced activation of Btk in mouse B cells was found to be unaffected by PI3K inhibitors or by a lack of PI3K. Consistent with this observation, PI3K(-/-) Btk(-/-) double- deficient mice had more severe defects than either single-mutant mouse. NF-kappaB activation along with Bcl-x(L) and cyclin D2 induction were severely blocked in both PI3K(-/-) and Btk(-/-) single-deficient B cells. Transgenic expression of Bcl-x(L) restored the development and BCR-induced proliferation of B cells in PI3K(-/-) mice. Our results indicate that PI3K and Btk have unique roles in proximal BCR signaling and that they have a common target further downstream in the activation of NF-kappaB.

引用

页码：280 / 286

页数：7

共 51 条

[1] An essential role for tyrosine kinase in the regulation of Bruton's B-cell apoptosis [J].