| First Author | Fu G | Year | 2017 |
| Journal | Eur J Immunol | Volume | 47 |
| Issue | 1 | Pages | 74-83 |
| PubMed ID | 27759161 | Mgi Jnum | J:246952 |
| Mgi Id | MGI:5923795 | Doi | 10.1002/eji.201646522 |
| Citation | Fu G, et al. (2017) Phospholipase Cgamma1 is required for pre-TCR signal transduction and pre-T cell development. Eur J Immunol 47(1):74-83 |
| abstractText | 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 Cgamma (PLCgamma) 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 PLCgamma1 is important for TCR-mediated signaling, development and T-cell activation, but the role of PLCgamma1 in pre-TCR signal transduction and pre-T cell development is not known. In this study, we demonstrated that PLCgamma1 expression level in pre-T cells was comparable to that in mature T cells. Deletion of PLCgamma1 prior to the pre-TCR signaling stage partially blocked the DN3 to DN4 transition and reduced thymic cellularity. We also demonstrated that deletion of PLCgamma1 impaired pre-T cell proliferation without affecting cell survival. Further study showed that deficiency of PLCgamma1 impaired pre-TCR mediated Ca2+ flux and Erk activation. Thus our studies demonstrate that PLCgamma1 is important for pre-TCR mediated signal transduction and pre-T cell development. |
