title: Phospholipase Cγ1 is required for pre-TCR signal transduction and pre-T cell development.
abstract: 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 this 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.
authors.affiliation: The Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, USA.
authors.forename: Guoping
authors.initials: G
authors.lastname: Fu
authors.affiliation: The Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Yu
authors.affiliation: The Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, USA.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: The Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, USA.
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: The Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, USA.|Interdisciplinary Program in Biomedical Science, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhu
authors.affiliation: The Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, USA.|Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Debra K
authors.initials: DK
authors.lastname: Newman
authors.affiliation: The Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, USA.|Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Demin
authors.initials: D
authors.lastname: Wang
authors.affiliation: The Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, USA.
authors.forename: Renren
authors.initials: R
authors.lastname: Wen
mesh_terms: D000818:Animals; D015415:Biomarkers; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression; D005838:Genotype; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D051966:Phospholipase C gamma / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D060168:Thymocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D048049:Extracellular Signal-Regulated MAP Kinases; D051966:Phospholipase C gamma; D002118:Calcium
keywords: Phospholipase Cγ1; Pre-T cell; Pre-TCR; Signal transduction; T-cell development