Suzuki Harumi, Matsuda Satoshi, Terauchi Yasuo, Fujiwara Mari, Ohteki Toshiaki, Asano Tomoichiro, Behrens Timothy W, Kouro Taku, Takatsu Kiyoshi, Kadowaki Takashi, Koyasu Shigeo
Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan.
Nat Immunol. 2003 Mar;4(3):280-6. doi: 10.1038/ni890. Epub 2003 Feb 3.
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-xL and cyclin D2 induction were severely blocked in both PI3K-/- and Btk-/- single-deficient B cells. Transgenic expression of Bcl-xL 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.
磷酸肌醇-3激酶（PI3K）被认为可激活酪氨酸激酶Btk。然而，通过对PI3K基因敲除小鼠和Btk基因敲除小鼠的分析发现，在小鼠B细胞中，B细胞抗原受体（BCR）诱导的Btk激活不受PI3K抑制剂或PI3K缺失的影响。与这一观察结果一致，PI3K基因敲除Btk基因敲除的双缺陷小鼠比任一单突变小鼠都有更严重的缺陷。在PI3K基因敲除和Btk基因敲除的单缺陷B细胞中，NF-κB激活以及Bcl-xL和细胞周期蛋白D2的诱导均被严重阻断。Bcl-xL的转基因表达恢复了PI3K基因敲除小鼠中B细胞的发育和BCR诱导的增殖。我们的结果表明，PI3K和Btk在近端BCR信号传导中具有独特作用，并且它们在NF-κB激活的更下游有一个共同靶点。
