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活化的 PLC-γ1 在 LAT 处被催化诱导，但活化的 PLC-γ1 定位于含有 LAT 和 TCR 的复合物两者处。

Activated PLC-γ1 is catalytically induced at LAT but activated PLC-γ1 is localized at both LAT- and TCR-containing complexes.

机构信息

Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States.

Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States.

出版信息

Cell Signal. 2014 Apr;26(4):797-805. doi: 10.1016/j.cellsig.2013.12.022. Epub 2014 Jan 8.

DOI:10.1016/j.cellsig.2013.12.022
PMID:24412752
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3935424/
Abstract

Phospholipase C-γ1 (PLC-γ1) is a key regulator of T cell receptor (TCR)-induced signaling. Activation of the TCR enhances PLC-γ1 enzymatic function, resulting in calcium influx and the activation of PKC family members and RasGRP. The current model is that phosphorylation of LAT tyrosine 132 facilitates the recruitment of PLC-γ1, leading to its activation and function at the LAT complex. In this study, we examined the phosphorylation kinetics of LAT and PLC-γ1 and the cellular localization of activated PLC-γ1. We observed that commencement of the phosphorylation of LAT tyrosine 132 and PLC-γ1 tyrosine 783 occurred simultaneously, supporting the current model. However, once begun, PLC-γ1 activation occurred more rapidly than LAT tyrosine 132. The association of LAT and PLC-γ1 was more transient than the interaction of LAT and Grb2 and a pool of activated PLC-γ1 translocated away from LAT to cellular structures containing the TCR. These studies demonstrate that LAT and PLC-γ1 form transient interactions that catalyze the activation of PLC-γ1, but that activated PLC-γ1 resides in both LAT and TCR clusters. Together, this work highlights that our current model is incomplete and the activation and function of PLC-γ1 in T cells is highly complex.

摘要

PLC-γ1（磷脂酶 C-γ1）是 T 细胞受体（TCR）诱导信号的关键调节因子。TCR 的激活增强了 PLC-γ1 的酶活性，导致钙离子内流以及 PKC 家族成员和 RasGRP 的激活。目前的模型是，LAT 酪氨酸 132 的磷酸化促进了 PLC-γ1 的募集，导致其在 LAT 复合物中被激活和发挥作用。在这项研究中，我们检查了 LAT 和 PLC-γ1 的磷酸化动力学以及激活的 PLC-γ1 的细胞定位。我们观察到，LAT 酪氨酸 132 和 PLC-γ1 酪氨酸 783 的磷酸化同时开始，支持了当前的模型。然而，一旦开始，PLC-γ1 的激活比 LAT 酪氨酸 132 发生得更快。LAT 和 PLC-γ1 的关联比 LAT 和 Grb2 的相互作用更短暂，并且池状的激活的 PLC-γ1 从 LAT 转位到包含 TCR 的细胞结构中。这些研究表明，LAT 和 PLC-γ1 形成短暂的相互作用，催化 PLC-γ1 的激活，但激活的 PLC-γ1 存在于 LAT 和 TCR 簇中。总之，这项工作强调了我们当前的模型是不完整的，PLC-γ1 在 T 细胞中的激活和功能非常复杂。

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