Direct inhibition of Brurton's tyrosine kinase by IBtk, a Btk-binding protein

被引：59

作者：

Liu, WM

Quinto, I

Chen, XN

Palmieri, C

Rabin, RL

Schwartz, OM

Nelson, DL

Scala, G ^{[1
]}

机构：

[1] Univ Catanzaro, Dept Clin & Expt Med, Sch Med, I-88100 Catanzaro, Italy

[2] Univ Naples Federico II, Sch Med, Dept Biochem & Biomed Technol, I-80131 Naples, Italy

[3] NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA

[4] NIAID, Biol Imaging Facil, NIH, Bethesda, MD 20892 USA

[5] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA

来源：

NATURE IMMUNOLOGY | 2001年 / 2卷 / 10期

关键词：

D O I：

10.1038/ni1001-939

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Bruton's tyrosine kinase (Btk) is required for human and mouse B cell development. Btk deficiency causes X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency in mice. Unlike Src proteins, Btk lacks a negative regulatory domain at the COOH terminus and may rely on cytoplasmic Btk-binding proteins to regulates its kinase activity by trans-inhibitor mechanisms. Consistent with this possibility, IBtk, which we identified as an inhibitor of Btk, bound to the PH domain of Btk. IBtk downregulated Btk kinase activity, Btk-mediated calcium mobilization and nuclear factor-kappaB-driven transcription. These results define a potential mechanism for the regulation of Btk function in B cells.

引用

页码：939 / 946

页数：8

共 52 条

[1] HIV-1 Tat induces the expression of the interleukin-6 (IL6) gene by binding to the IL6 leader RNA and by interacting with CAAT enhancer-binding protein beta (NF-IL6) transcription factors [J].