Qiu Y, Kung H J
Department of Laboratory Medicine and Pathology and Cancer Center, 420 Delaware Street SE, University of Minnesota, Minneapolis, MN 55455, USA.
Oncogene. 2000 Nov 20;19(49):5651-61. doi: 10.1038/sj.onc.1203958.
The Btk family kinases represent new members of non-receptor tyrosine kinases, which include Btk/Atk, Itk/Emt/Tsk, Bmx/Etk, and Tec. They are characterized by having four structural modules: PH (pleckstrin homology) domain, SH3 (Src homology 3) domain, SH2 (Src homology 2) domain and kinase (Src homology 1) domain. Increasing evidence suggests that, like Src-family kinases, Btk family kinases play central but diverse modulatory roles in various cellular processes. They participate in signal transduction in response to virtually all types of extracellular stimuli which are transmitted by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen-receptors and integrins. They are regulated by many non-receptor tyrosine kinases such as Src, Jak, Syk and FAK family kinases. In turn, they regulate many of major signaling pathways including those of PI3K, PLCgamma and PKC. Both genetic and biochemical approaches have been used to dissect the signaling pathways and elucidate their roles in growth, differentiation and apoptosis. An emerging new role of this family of kinases is cytoskeletal reorganization and cell motility. The physiological importance of these kinases was amply demonstrated by their link to the development of immunodeficiency diseases, due to germ-line mutations. The present article attempts to review the structure and functions of Btk family kinases by summarizing our current knowledge on the interacting partners associated with the different modules of the kinases and the diverse signaling pathways in which they are involved.
Btk家族激酶是非受体酪氨酸激酶的新成员，包括Btk/Atk、Itk/Emt/Tsk、Bmx/Etk和Tec。它们的特征是具有四个结构模块：PH（普列克底物蛋白同源）结构域、SH3（Src同源3）结构域、SH2（Src同源2）结构域和激酶（Src同源1）结构域。越来越多的证据表明，与Src家族激酶一样，Btk家族激酶在各种细胞过程中发挥着核心但多样的调节作用。它们参与几乎所有类型细胞外刺激的信号转导，这些刺激由生长因子受体、细胞因子受体、G蛋白偶联受体、抗原受体和整合素传递。它们受许多非受体酪氨酸激酶如Src、Jak、Syk和FAK家族激酶的调节。反过来，它们调节许多主要的信号通路，包括PI3K、PLCγ和PKC的信号通路。遗传和生化方法都已被用于剖析信号通路并阐明它们在生长、分化和凋亡中的作用。这个激酶家族一个新出现的作用是细胞骨架重组和细胞运动。由于种系突变，这些激酶与免疫缺陷疾病的发生有关，这充分证明了它们的生理重要性。本文试图通过总结我们目前关于与激酶不同模块相关的相互作用伙伴以及它们所涉及的多样信号通路的知识，来综述Btk家族激酶的结构和功能。
