Molecular Modeling Lab-MML, Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab 147002, India.
Eur J Pharm Sci. 2012 Oct 9;47(3):574-88. doi: 10.1016/j.ejps.2012.07.013. Epub 2012 Jul 20.
Interleukin-2 inducible T-cell kinase (ITK), a member of Tec family of non-receptor protein tyrosine kinases plays a domineering role in the T-cell development, differentiation and production of pro-inflammatory cytokines such as IL-2, IL-4, IL-5, IL-10, IL-13 and IL-17. This kinase is also an important contributor in Th 2 cells mediated autoimmune and allergic disease conditions, e.g. psoriasis, atopic dermatitis and allergic asthma. ITK modulates T-cell signaling by activating PLCγ1 and regulating the extent of Ca²⁺ flux. It contributes in prolific T-cell responses by maintaining cellular adhesion and cytoskeleton reorganization via actin polymerization and integrin binding. This review article describes the structure of ITK and its role in T-cell signaling. In addition to this, data regarding small molecule inhibitors of ITK has also been reviewed from different papers and patents published.
白细胞介素-2 诱导的 T 细胞激酶(ITK)是 Tec 家族非受体蛋白酪氨酸激酶的成员,在 T 细胞发育、分化和产生白细胞介素 2(IL-2)、白细胞介素 4(IL-4)、白细胞介素 5(IL-5)、白细胞介素 10(IL-10)、白细胞介素 13(IL-13)和白细胞介素 17(IL-17)等促炎细胞因子方面发挥着主导作用。这种激酶也是 Th2 细胞介导的自身免疫和过敏疾病的重要贡献者,如银屑病、特应性皮炎和过敏性哮喘。ITK 通过激活 PLCγ1 和调节钙流的程度来调节 T 细胞信号转导。它通过肌动蛋白聚合和整合素结合来维持细胞黏附和细胞骨架重组,促进丰富的 T 细胞反应。本文综述了 ITK 的结构及其在 T 细胞信号转导中的作用。此外,还从不同的论文和专利出版物中综述了有关 ITK 的小分子抑制剂的数据。