鸟嘌呤核苷酸交换因子
CD28
生物
细胞生物学
克隆缺失
T细胞
T细胞受体
MAPK/ERK通路
信号转导
癌症研究
遗传学
免疫系统
作者
Ya-Ting Chang,Praveen Manivannan,Abbas Doosti,Philip E. Lapinski,Chen D,Jeroen P. Roose,Philip D. King
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2023-08-11
卷期号:211 (6): 917-922
标识
DOI:10.4049/jimmunol.2300138
摘要
Ras guanine nucleotide-releasing protein 1 (Rasgrp1) is a Ras guanine nucleotide exchange factor that participates in the activation of the Ras-ERK signaling pathway in developing T cells and is required for efficient thymic T cell positive selection. However, the role of Rasgrp1 in mature peripheral T cells has not been definitively addressed, in part because peripheral T cells from constitutive Rasgrp1-deficient mice show an abnormal activated phenotype. In this study, we generated an inducible Rasgrp1-deficient mouse model to allow acute disruption of Rasgrp1 in peripheral CD4+ T cells in the context of normal T cell development. TCR/CD28-mediated activation of Ras-ERK signaling was blocked in Rasgrp1-deficient peripheral CD4+ T cells. Furthermore, Rasgrp1-deficient CD4+ T cells were unable to synthesize IL-2 and the high-affinity IL-2R and were unable to proliferate in response to TCR/CD28 stimulation. These findings highlight an essential function for Rasgrp1 for TCR/CD28-induced Ras-ERK activation in peripheral CD4+ T cells.
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