Lopez M, Aoubala M, Jordier F, Isnardon D, Gomez S, Dubreuil P
INSERM U.119, Unité de Cancérologie et Thérapeutique Expérimentales, Marseille, France.
Blood. 1998 Dec 15;92(12):4602-11.
We have recently described Poliovirus Receptor Related 2 (PRR2), a new cell surface molecule homologous to the poliovirus receptor (PVR/CD155). Both molecules are transmembrane glycoproteins belonging to the Ig superfamily (IgSF). They contain 3 Ig domains of V, C2, and C2 types in their extracellular regions that share 51% aa identity. The PRR2 gene encodes two mRNA isoforms of 3.0 kb (hPRR2 [short form]) and 4.4 kb (hPRR2delta [long form]), both widely expressed in human tissues, including hematopoietic cells. To further characterize PRR2 expression during hematopoiesis and to analyze its function, we have developed a monoclonal antibody (MoAb) directed against its extracellular region (R2.477). PRR2 was expressed in 96% of the CD34(+), 88% of the CD33(+), and 95% of the CD14(+) hematopoietic lineages and faintly in the CD41 compartment. Ectopic expression of both PRR2 cDNAs induced marked cell aggregation. A soluble chimeric receptor construct with the Fc fragment of human IgG1 (PRR2-Fc) as well as a fab fragment of the anti-PRR2 MoAb (R2.477) inhibit aggregation. PRR2-Fc binds specifically to PRR2-expressing cells. These results suggest that PRR2 is a homophilic adhesion receptor. PRR2 was also expressed at the surface of endothelial cells at the intercellular junctions of adjacent cells but not at the free cellular edges. Homophilic interactions are associated with dimerization of isoforms of PRR2 and lead to the tyrosine phosphorylation of PRR2delta. Altogether, these results suggest that homophilic properties of PRR2 could participate to the regulation of hematopoietic/endothelial cell functions.
我们最近描述了脊髓灰质炎病毒受体相关2（PRR2），一种与脊髓灰质炎病毒受体（PVR/CD155）同源的新细胞表面分子。这两种分子都是属于免疫球蛋白超家族（IgSF）的跨膜糖蛋白。它们在细胞外区域含有3个V、C2和C2型免疫球蛋白结构域，氨基酸同源性为51%。PRR2基因编码两种mRNA异构体，分别为3.0 kb（hPRR2[短形式]）和4.4 kb（hPRR2delta[长形式]），二者在包括造血细胞在内的人体组织中广泛表达。为了进一步表征PRR2在造血过程中的表达并分析其功能作用，我们开发了一种针对其细胞外区域的单克隆抗体（MoAb，R2.477）。PRR2在96%的CD34(+)、88%的CD33(+)和95%的CD14(+)造血谱系中表达，在CD41区室中表达较弱。两种PRR2 cDNA的异位表达均诱导明显的细胞聚集。带有人类IgG1 Fc片段的可溶性嵌合受体构建体（PRR2-Fc）以及抗PRR2单克隆抗体（R2.477）的fab片段可抑制聚集。PRR2-Fc特异性结合表达PRR2的细胞。这些结果表明PRR2是一种同源性黏附受体。PRR2也表达于相邻细胞间连接处的内皮细胞表面，但在游离的细胞边缘不表达。同源性相互作用与PRR2异构体的二聚化相关，并导致PRR2delta的酪氨酸磷酸化。总之，这些结果表明PRR2的同源性特性可能参与造血/内皮细胞功能的调节。
