T细胞免疫球蛋白和粘蛋白结构域-1介导的T细胞活化需要磷酸肌醇3激酶的募集和激活。

T cell Ig and mucin domain-1-mediated T cell activation requires recruitment and activation of phosphoinositide 3-kinase.

作者信息

de Souza Anjali J, Oak Jean S, Jordanhazy Ryan, DeKruyff Rosemarie H, Fruman David A, Kane Lawrence P

机构信息

Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.

出版信息

J Immunol. 2008 May 15;180(10):6518-26. doi: 10.4049/jimmunol.180.10.6518.

Ligation of the transmembrane protein T cell Ig and mucin domain (Tim)-1 can costimulate T cell activation. Agonistic Abs to Tim-1 are also capable of inducing T cell activation without additional stimuli. However, little is known about the biochemical mechanisms underlying T cell stimulation or costimulation through Tim-1. We show that a tyrosine in Tim-1 becomes phosphorylated in a lck-dependent manner, whereupon it can directly recruit p85 adaptor subunits of PI3K. This results in PI3K activation, which is required for Tim-1 function. We also provide genetic evidence that p85 expression is required for optimal Tim-1 function. Thus, we describe a pathway from Tim-1 tyrosine phosphorylation to the PI3K signaling pathway, which appears to be a major effector of Tim-1-mediated T cell activation.

跨膜蛋白T细胞免疫球蛋白和粘蛋白结构域（Tim）-1的交联可共刺激T细胞活化。针对Tim-1的激动性抗体也能够在无额外刺激的情况下诱导T细胞活化。然而，关于通过Tim-1刺激或共刺激T细胞的生化机制知之甚少。我们发现Tim-1中的一个酪氨酸以依赖Lck的方式发生磷酸化，随后它可直接募集PI3K的p85衔接亚基。这导致PI3K活化，而这是Tim-1发挥功能所必需的。我们还提供了遗传学证据，表明p85表达是Tim-1发挥最佳功能所必需的。因此，我们描述了一条从Tim-1酪氨酸磷酸化到PI3K信号通路的途径，这似乎是Tim-1介导的T细胞活化的主要效应途径。