Conformational switches that control the TEC kinase – PLCγ signaling axis

IF 3.5 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Structural Biology: X Pub Date : 2022-01-01 DOI:10.1016/j.yjsbx.2022.100061
Jacques Lowe, Raji E. Joseph, Amy H. Andreotti
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引用次数: 5

Abstract

Cell surface receptors such as the T-cell receptor (TCR) and B-cell receptor (BCR) engage with external stimuli to transmit information into the cell and initiate a cascade of signaling events that lead to gene expression that drives the immune response. At the heart of controlling T- and B-cell cell signaling, phospholipase Cγ hydrolyzes membrane associated PIP2, leading to generation of the second messengers IP3 and DAG. These small molecules trigger mobilization of intracellular Ca2+ and promote transcription factor transport into the nucleus launching the adaptive immune response. The TEC family kinases are responsible for phosphorylating and activating PLCγ, and our group aims to understand mechanisms that regulate immune cell signal transduction by focusing on this kinase/phospholipase axis in T-cells and B-cells. Here, we review the current molecular level understanding of how the TEC kinases (ITK and BTK) and PLCγ1/2 are autoinhibited prior to activation of cell surface receptors, how TEC kinases are activated to specifically recognize the PLCγ substrate, and how conformational changes induced by phosphorylation trigger PLCγ activation.

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控制TEC激酶- PLCγ信号轴的构象开关
细胞表面受体,如t细胞受体(TCR)和b细胞受体(BCR)参与外部刺激,将信息传递到细胞中,并启动一系列信号事件,导致驱动免疫反应的基因表达。在控制T细胞和b细胞信号传导的核心,磷脂酶Cγ水解膜相关的PIP2,导致第二信使IP3和DAG的产生。这些小分子触发细胞内Ca2+的动员,促进转录因子转运到细胞核,启动适应性免疫反应。TEC家族激酶负责磷酸化和激活PLCγ,我们的研究小组旨在通过关注t细胞和b细胞中的这种激酶/磷脂酶轴来了解调节免疫细胞信号转导的机制。在这里,我们回顾了目前对TEC激酶(ITK和BTK)和PLCγ1/2如何在细胞表面受体激活之前被自抑制的分子水平的理解,TEC激酶如何被激活以特异性识别PLCγ底物,以及磷酸化诱导的构象变化如何触发PLCγ激活。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Structural Biology: X
Journal of Structural Biology: X Biochemistry, Genetics and Molecular Biology-Structural Biology
CiteScore
6.50
自引率
0.00%
发文量
20
审稿时长
62 days
期刊最新文献
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