Kawakami Y, Kitaura J, Hata D, Yao L, Kawakami T
Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
J Leukoc Biol. 1999 Mar;65(3):286-90. doi: 10.1002/jlb.65.3.286.
Bruton's tyrosine kinase (Btk) plays crucial roles in B cell differentiation as well as mast cell activation through the high-affinity IgE receptor (FcepsilonRI). Defects in the btk gene lead to agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Mast cells from xid and btk null mice exhibit mild defects in degranulation and severe impairments in the production of proinflammatory cytokines upon FcepsilonRI cross-linking. Recent studies demonstrated the role of Btk in a sustained increase in intracellular calcium concentrations in response to antigen receptor stimulation. Btk is also involved in the activation of stress-activated protein kinases, JNK/SAPK1/2, and thereby regulates c-Jun and other transcription factors that are important in cytokine gene activation. Regulation of the JNK/SAPK activation pathway by Btk may be related to the proapoptotic function of Btk in the programmed cell death in these hematopoietic cells.
布鲁顿酪氨酸激酶（Btk）通过高亲和力IgE受体（FcepsilonRI）在B细胞分化以及肥大细胞激活过程中发挥关键作用。btk基因缺陷导致人类无丙种球蛋白血症（XLA）和小鼠X连锁免疫缺陷（xid）。来自xid和btk基因敲除小鼠的肥大细胞在脱颗粒方面表现出轻微缺陷，并且在FcepsilonRI交联后促炎细胞因子的产生受到严重损害。最近的研究表明，Btk在响应抗原受体刺激时细胞内钙浓度的持续增加中发挥作用。Btk还参与应激激活蛋白激酶JNK/SAPK1/2的激活，从而调节c-Jun和其他在细胞因子基因激活中重要的转录因子。Btk对JNK/SAPK激活途径的调节可能与Btk在这些造血细胞程序性细胞死亡中的促凋亡功能有关。
