PVR binds CD226

NK cells express adhesion molecules that allow interaction with their tumour targets, promoting their lysis.<p><p>For instance, the activating receptor CD226 is known to be involved in cytotoxic lymphocyte formation, as well as platelet adhesion to the endothelium. The cytoplasmic domain of CD226 contains binding motifs for members of the band 4.1 family of proteins, and for members of the membrane-associated guanylate kinase homolog (MAGUK) family. These proteins connect the CD226 receptor to the cytoskeleton and may promote clustering with LFA-1 integrin (also discussed in this pathway), which is known to participate in CD226's signaling cascade. CD226 plays a role in transendothelial migration, where it facilitates adherence to endothelial cells and migration between cell junctions. <p><p>Nectin-2 binds CD226. It is ubiquitously expressed in cells of various tissues, especially in epithelial cells, neurons and fibroblasts. Like many other nectin and Necl proteins, nectin-2 serves as a viral entry receptor for alpha-herpesviruses including herpes simplex virus (HSV-1 and HSV-2). The other CD226 ligand, Necl-5, was initially identified as a receptor for poliovirus.<p><p>CD96, another ligand for Necl-5, is strongly upregulated in activated NK cells.<p><p>CRTAM is similarly up-regulated, and has been shown to to bind Necl-2, promoting NK cell cytotoxicity towards otherwise poorly immunogenic targets.

自然杀伤细胞表达粘附分子，使其能够与其肿瘤靶标相互作用，从而促进其裂解。例如，已知活化受体CD226参与了细胞毒性淋巴细胞的形成，以及血小板与内皮细胞的粘附。CD226的胞质域含有与4.1蛋白家族成员以及与膜结合型鸟苷酸激酶同源物（MAGUK）家族成员的结合基序。这些蛋白将CD226受体与细胞骨架相连接，并可能促进其与LFA-1整合素的聚集（该整合素在本途径中亦有所论述），LFA-1整合素已知参与CD226的信号转导级联反应。CD226在跨内皮迁移中发挥作用，它促进了内皮细胞的粘附以及细胞间隙的迁移。<p><p>nectin-2与CD226结合。该蛋白在多种组织细胞中广泛表达，尤其在上皮细胞、神经元和成纤维细胞中。与许多其他nectin和Necl蛋白类似，nectin-2充当了α-疱疹病毒（包括单纯疱疹病毒HSV-1和HSV-2）的病毒进入受体。CD226的另一配体Necl-5最初被鉴定为脊髓灰质炎病毒的受体。<p><p>CD96是Necl-5的另一配体，在活化的自然杀伤细胞中显著上调。<p><p>CRTAM亦呈现上调趋势，研究表明其能与Necl-2结合，从而促进自然杀伤细胞对原本免疫原性较差的靶标实施细胞毒性作用。