Marmor M D, Julius M
Department of Immunology, University of Toronto, Ontario, Canada.
J Biol Regul Homeost Agents. 2000 Apr-Jun;14(2):99-115.
Many glycosylphosphatidyl-inositol-anchored proteins (GPI-AP) are expressed on T lymphocytes. Ligand or mAb-mediated aggregation of all GPI-AP tested to date results in the initiation of signal transduction pathways via the activation of src family protein tyrosine kinases. Src family kinases co-localise with GPI-AP in specialised sub-domains of the plasma membrane, referred to as detergent insoluble membrane microdomains (DIGS), which are thought to function as signalling platforms. GPI-AP may play a role in the regulation of T cell clonal expansion and effector functions at multiple levels, including the initiation of T cell activation through the antigen receptor complex, the regulation of ongoing responses supported by persisting antigen, as well as proliferative responses to the major T cell growth factor, IL-2. Evidence supporting the role of GPI-AP in the regulation of T cell development, activation and homeostasis is discussed, as well as insights provided by studies in humans and mice lacking GPI-AP.
许多糖基磷脂酰肌醇锚定蛋白(GPI-AP)在T淋巴细胞上表达。迄今为止,所有经测试的GPI-AP的配体或单克隆抗体介导的聚集都会通过src家族蛋白酪氨酸激酶的激活引发信号转导途径。Src家族激酶与GPI-AP在质膜的特殊亚结构域中共定位,称为去污剂不溶性膜微结构域(DIGS),被认为作为信号平台发挥作用。GPI-AP可能在多个水平上参与T细胞克隆扩增和效应功能的调节,包括通过抗原受体复合物启动T细胞活化、由持续存在的抗原支持的正在进行的反应的调节,以及对主要T细胞生长因子IL-2的增殖反应。本文讨论了支持GPI-AP在T细胞发育、活化和稳态调节中作用的证据,以及缺乏GPI-AP的人类和小鼠研究提供的见解。