布鲁顿酪氨酸激酶通过一种涉及磷脂酶C-γ2的机制，在B细胞抗原受体结合后将核因子κB靶向bcl-x启动子。

Bruton's tyrosine kinase targets NF-kappaB to the bcl-x promoter via a mechanism involving phospholipase C-gamma2 following B cell antigen receptor engagement.

作者信息

Petro James B, Castro Iris, Lowe John, Khan Wasif N

机构信息

Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.

出版信息

FEBS Lett. 2002 Dec 4;532(1-2):57-60. doi: 10.1016/s0014-5793(02)03623-2.

DOI:10.1016/s0014-5793(02)03623-2

PMID:12459462

Abstract

Disruption of Bruton's tyrosine kinase (BTK) function leads to x-linked immunodeficiency (xid) in mice. BTK-deficient (btk(-/-)) B cells are defective for survival. Prior studies show that BTK is required for the induction of Bcl-x(L) following B cell antigen receptor (BCR) engagement. However, the mechanism underlying Bcl-x(L) induction in response to BCR ligation remains unresolved. We now demonstrate that BTK regulates bcl-x expression by transcriptional control in response to BCR engagement. BTK targets nuclear factor-kappaB (NF-kappaB) to activate the bcl-x promoter via a phospholipase C-gamma2 (PLC-gamma2)-dependent mechanism. Perturbation of the BTK/PLC-gamma2/NF-kappaB signaling axis likely contributes to the defective expression of bcl-x and compromised survival of xid B cells.

摘要

布鲁顿酪氨酸激酶（BTK）功能的破坏会导致小鼠出现X连锁免疫缺陷（xid）。BTK缺陷型（btk(-/-)）B细胞在存活方面存在缺陷。先前的研究表明，B细胞抗原受体（BCR）激活后诱导Bcl-x(L)需要BTK。然而，BCR连接后Bcl-x(L)诱导的潜在机制仍未明确。我们现在证明，BTK通过转录控制对BCR激活作出反应来调节bcl-x的表达。BTK靶向核因子-κB（NF-κB），通过磷脂酶C-γ2（PLC-γ2）依赖性机制激活bcl-x启动子。BTK/PLC-γ2/NF-κB信号轴的紊乱可能导致bcl-x表达缺陷以及xid B细胞存活受损。