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II型磷脂酰肌醇4激酶β与CD4-p56lck复合物相关,并参与CD4受体信号传导。

Type II PtdIns 4-kinase β associates with CD4-p56lck complex and is involved in CD4 receptor signaling.

作者信息

Sinha Ranjeet Kumar, Bojjireddy Naveen, Kanojia Deepak, Subrahmanyam Gosukonda

机构信息

Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, 400076, India,

出版信息

Mol Cell Biochem. 2014 Oct;395(1-2):231-9. doi: 10.1007/s11010-014-2129-9. Epub 2014 Jun 28.

Abstract

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.

摘要

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。

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