BLNK介导依赖Syk的Btk激活。
BLNK mediates Syk-dependent Btk activation.
作者信息
Baba Y, Hashimoto S, Matsushita M, Watanabe D, Kishimoto T, Kurosaki T, Tsukada S
机构信息
Department of Molecular Medicine, Osaka University Medical School, 2-2 Yamada-oka, Suita City, Osaka 565-0871, Japan.
出版信息
Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2582-6. doi: 10.1073/pnas.051626198. Epub 2001 Feb 13.
Btk is a critical molecule in B cell antigen receptor (BCR)-coupled signaling, and its activity is regulated by Lyn and Syk. Although the molecular mechanism of Lyn-dependent Btk activation has been investigated, that of Syk-dependent Btk activation has remained unidentified. We have demonstrated that BLNK mediates Syk-dependent Btk activation. In a reconstitution cell system, coexpression of BLNK allows Syk to phosphorylate Btk on its tyrosine 551, leading to the enhancement of Btk activity. This phosphorylation depends on the interaction of Btk and BLNK by means of the Btk-Src homology 2 domain. The existence of such an activation mechanism is supported by the observation that the BCR-induced Btk phosphorylation and activation are significantly reduced in BLNK-deficient B cells as well as in Syk-deficient B cells. Although previous observations have identified the function of BLNK as the linker that integrates the action of Btk and Syk into downstream effectors such as phospholipase Cgamma2, our present study indicates another function of BLNK that connects the activity of Syk to that of Btk.
布鲁顿酪氨酸激酶（Btk）是B细胞抗原受体（BCR）偶联信号传导中的关键分子，其活性受Lyn和Syk调节。尽管Lyn依赖性Btk激活的分子机制已得到研究，但Syk依赖性Btk激活的机制仍不清楚。我们已经证明B细胞连接蛋白（BLNK）介导Syk依赖性Btk激活。在重组细胞系统中，BLNK的共表达使Syk能够磷酸化Btk的酪氨酸551，从而增强Btk活性。这种磷酸化依赖于Btk和BLNK通过BtkSrc同源2结构域的相互作用。BCR诱导的Btk磷酸化和激活在BLNK缺陷型B细胞以及Syk缺陷型B细胞中显著降低，这一观察结果支持了这种激活机制的存在。尽管先前的观察已经确定BLNK的功能是作为将Btk和Syk的作用整合到下游效应分子（如磷脂酶Cγ2）中的接头，但我们目前的研究表明BLNK还有另一个功能，即将Syk的活性与Btk的活性联系起来。
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