Geng Xin, Tang Ren-Hong, Law S K Alex, Tan Suet-Mien
Division of Molecular and Cell Biology, School of Biological Sciences, Nanyang Technological University, Singapore.
Immunology. 2005 Jul;115(3):347-57. doi: 10.1111/j.1365-2567.2005.02175.x.
Leucocyte adhesion receptor integrin CD11aCD18 and the transmembrane receptor-like protein tyrosine phosphatase (RPTP) CD45 mediate immune synapse formation and signalling during antigen presentation. Previous cocapping studies on human naïve T cells demonstrate an interaction between CD11aCD18 and CD45. CD45 cross-linking also has an effect on the ligand-binding activity of CD11aCD18. However, the mode of interaction between CD11aCD18 and CD45 remains unclear. Herein, yeast two-hybrid analysis identified a partial CD45 cytoplasmic tail interacting with that of CD11a. The CD45 cytoplasmic tail comprises a membrane proximal (Mp) region, protein tyrosine phosphatase domain 1 (D1), spacer, D2, and carboxyl terminus. CD45 Mp-D1 was found to be the main interacting region for the CD11a cytoplasmic tail. In contrast, the full-length CD45 cytoplasmic tail interacted weakly with that of CD11a. It has been reported that CD45 Mp-D1 but not the full-length cytoplasmic tail forms a homodimer whose enzymatic activity is inhibited. Our in vitro binding and enzymatic assays showed that the homodimeric CD45 cytoplasmic tail interacts with that of CD11a. The biological function of CD45 dimerization and its association with CD11a remains to be investigated.
白细胞黏附受体整合素CD11aCD18和跨膜受体样蛋白酪氨酸磷酸酶（RPTP）CD45在抗原呈递过程中介导免疫突触的形成和信号传导。先前对人初始T细胞的共帽研究表明CD11aCD18与CD45之间存在相互作用。CD45交联也对CD11aCD18的配体结合活性有影响。然而，CD11aCD18与CD45之间的相互作用模式仍不清楚。在此，酵母双杂交分析鉴定出部分CD45胞质尾与CD11a的胞质尾相互作用。CD45胞质尾包括膜近端（Mp）区域、蛋白酪氨酸磷酸酶结构域1（D1）、间隔区、D2和羧基末端。发现CD45 Mp-D1是与CD11a胞质尾相互作用的主要区域。相比之下，全长CD45胞质尾与CD11a胞质尾的相互作用较弱。据报道，CD45 Mp-D1而非全长胞质尾形成同二聚体，其酶活性受到抑制。我们的体外结合和酶活性测定表明，同二聚体CD45胞质尾与CD11a胞质尾相互作用。CD45二聚化的生物学功能及其与CD11a的关联仍有待研究。
