Phospholipase Cγ1 is required for pre-TCR signal transduction and pre-T cell development.

Phospholipase Cγ1 is required for pre-TCR signal transduction and pre-T cell development.
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DOI:
10.1002/eji.201646522
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发表时间:
2017-01
影响因子:
5.4
通讯作者:
Wen R
Wen R
中科院分区:
医学3区
文献类型:
--
作者:
Fu G;Yu M;Chen Y;Zheng Y;Zhu W;Newman DK;Wang D;Wen R

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Pre-T cell receptor (TCR) signaling is required for pre-T cell survival, proliferation, and differentiation from the CD4 and CD8 double negative (DN) to the double positive (DP) stage. However, the pre-TCR signal transduction pathway is not fully understood and the signaling molecules involved have not been completely identified. Phospholipase Cγ (PLCγ) 1 is an important signaling molecule that generates two second messengers, diacylglycerol and inositol 1,4,5-trisphosphate, that are important to mediate PKC activation and intracellular Ca2+ flux in many signaling pathways. Previously, we have shown that PLCγ1 is important for TCR-mediated signaling, development and T-cell activation, but, the role of PLCγ1 in pre-TCR signal transduction and pre-T cell development is not known. In the current study, we demonstrated that PLCγ1 expression level in pre-T cells was comparable to that in mature T cells. Deletion of PLCγ1 prior to the pre-TCR signaling stage partially blocked the DN3 to DN4 transition and reduced thymic cellularity. We also demonstrated that deletion of PLCγ1 impaired pre-T cell proliferation without affecting cell survival. Further study showed that deficiency of PLCγ1 impaired pre-TCR mediated Ca2+ flux and Erk activation. Thus our studies demonstrate that PLCγ1 is important for pre-TCR mediated signal transduction and pre-T cell development.
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