Notch信号通路
生物
细胞生物学
Hes3信号轴
T细胞
磷酸化
T细胞受体
信号转导
CD28
过继性细胞移植
蛋白激酶B
免疫学
免疫系统
作者
Todd N. Eagar,Qizhi Tang,Michael S. Wolfe,Yiping He,Warren S. Pear,Jeffrey A. Bluestone
出处
期刊:Immunity
[Elsevier]
日期:2004-04-01
卷期号:20 (4): 407-415
被引量:150
标识
DOI:10.1016/s1074-7613(04)00081-0
摘要
Notch signaling has been identified as an important regulator of leukocyte differentiation and thymic maturation. Less is known about the role of Notch signaling in regulating mature T cells. We examined the role of Notch 1 in regulating peripheral T cell activity in vitro and in vivo. Coligation of Notch 1 together with TCR and CD28 resulted in a dramatic inhibition of T cell activation, proliferation, and cytokine production. This effect was dependent on presenilin activity and induced the expression of HES-1, suggestive of Notch 1 signaling. Biochemical analysis demonstrated an inhibition of AKT and GSK3beta phosphorylation following Notch 1 engagement while other biochemical signals such as TCR and ERK phosphorylation remained intact. Similar effects were observed in vivo in an adoptive transfer model. Therefore, Notch 1 signaling may play an important role in regulating naive T cell activation and homeostasis.
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