Activated PLC-γ1 is catalytically induced at LAT but activated PLC-γ1 is localized at both LAT- and TCR-containing complexes.
Activated PLC-γ1 is catalytically induced at LAT but activated PLC-γ1 is localized at both LAT- and TCR-containing complexes.
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DOI：
10.1016/j.cellsig.2013.12.022
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发表时间：
2014-04
影响因子：
4.8
通讯作者：
Houtman JC
中科院分区：
文献类型：
--
作者：
Cruz-Orcutt N;Vacaflores A;Connolly SF;Bunnell SC;Houtman JC
磷脂酶C-γ1（PLC-γ1）是T细胞受体（TCR）诱导的信号传导的关键调节因子。TCR的活化增强PLC-γ1酶功能，导致钙内流和PKC家族成员和RasGRP的活化。目前的模型是LAT酪氨酸132的磷酸化促进PLC-γ1的募集，导致其在LAT复合物中的活化和功能。在这项研究中，我们研究了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的磷酸化同时发生，支持当前模型。然而，一旦开始，PLC-γ1活化发生得比LAT酪氨酸132更快。LAT和PLC-γ1的结合比LAT和Grb 2的相互作用更短暂，并且活化的PLC-γ1的池从LAT易位到含有TCR的细胞结构。这些研究表明，LAT和PLC-γ1形成催化PLC-γ1活化的瞬时相互作用，但活化的PLC-γ1存在于LAT和TCR簇中。总之，这项工作强调了我们目前的模型是不完整的，PLC-γ1在T细胞中的激活和功能是高度复杂的。
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.
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影响因子：
4.4
作者：
Houtman, JCD;Houghtling, RA;Samelson, LE
通讯作者：
Samelson, LE
影响因子：
4.8
作者：
Beach, Dvora;Gonen, Ronnie;Yablonski, Deborah
通讯作者：
Yablonski, Deborah
DOI：
10.1073/pnas.92.11.5042
发表时间：
1995-05-23
影响因子：
11.1
作者：
MCKEITHAN, TW
通讯作者：
MCKEITHAN, TW
DOI：
10.1073/pnas.101113698
发表时间：
2001-05-08
影响因子：
11.1
作者：
Chan, C;George, AJT;Stark, J
通讯作者：
Stark, J
影响因子：
4.4
作者：
Kortum, Robert L.;Rouquette-Jazdanian, Alexandre K.;Sommers, Connie L.
通讯作者：
Sommers, Connie L.