Sinha Ranjeet Kumar, Bojjireddy Naveen, Kanojia Deepak, Subrahmanyam Gosukonda
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, 400076, India,
Mol Cell Biochem. 2014 Oct;395(1-2):231-9. doi: 10.1007/s11010-014-2129-9. Epub 2014 Jun 28.
Type II phosphatidylinositol (PtdIns) 4-kinases are involved in the synthesis of PtdIns 4-phosphates and modulate various cell functions like, intracellular signaling, cytoskeletal rearrangements, vesicular trafficking, and pathogen invasion. In CD3 receptor activated T cells, a type II PtdIns 4-kinase β is recruited to CD3 receptor zeta and plays a role in intracellular calcium release and probably in actin cytoskeleton reorganization. T cell receptor mediated activation is supported by CD4 receptor. The role of type II PtdIns 4-kinase β in CD4 receptor-mediated signaling was addressed in the present manuscript. Crosslinking of CD4 receptors with monoclonal antibodies showed an increase in CD4-associated PtdIns 4-kinase activity and requires p56(lck) activity. Biochemical characterization suggests that it belongs to type II PtdIns 4-kinase family. shRNA mediated knockdown of type II PtdIns 4-kinase β showed abrogation of CD4 receptor induced intracellular calcium release. These results suggest that type II PtdIns 4-kinase β plays an integral part in CD4 receptor-mediated signaling.
II型磷脂酰肌醇(PtdIns)4-激酶参与PtdIns 4-磷酸的合成,并调节多种细胞功能,如细胞内信号传导、细胞骨架重排、囊泡运输和病原体入侵。在CD3受体激活的T细胞中,II型PtdIns 4-激酶β被招募到CD3受体ζ链,并在细胞内钙释放中发挥作用,可能还参与肌动蛋白细胞骨架的重组。T细胞受体介导的激活由CD4受体支持。本论文探讨了II型PtdIns 4-激酶β在CD4受体介导的信号传导中的作用。用单克隆抗体交联CD4受体显示,CD4相关的PtdIns 4-激酶活性增加,且需要p56(lck)活性。生化特性表明它属于II型PtdIns 4-激酶家族。shRNA介导的II型PtdIns 4-激酶β敲低显示,CD4受体诱导的细胞内钙释放被消除。这些结果表明,II型PtdIns 4-激酶β在CD4受体介导的信号传导中起不可或缺的作用。