Sobocki T, Sobocka M B, Babinska A, Ehrlich Y H, Banerjee P, Kornecki E
Program in Neuroscience and Department of Chemistry, College of Staten Island, CUNY, 2800 Victory Blvd., 6S-326, Staten Island, NY 10314, USA.
Gene. 2006 Jan 17;366(1):128-44. doi: 10.1016/j.gene.2005.08.025. Epub 2005 Dec 5.
The F11-receptor (F11R) (a.k.a. JAM-1, JAM-A, CD321) is a cell adhesion molecule of the immunoglobulin superfamily involved in platelet adhesion, secretion and aggregation. In addition, the F11R plays a critical role in the function of endothelial cells and in platelet adhesion to inflamed endothelium. In the present study, we used partial sequences of the human F11R gene, F11R cDNAs, and information in unannotated human genome databases, to delineate the F11R gene. We found that the F11R gene is composed of 13 exons (E1a, 1b, 1c, E1-E10) encoding two groups of mRNAs differing in length and sequence at their 5' UTRs, referred to as type 1 and type 2 messages. Type 1 cDNAs are shorter at the 5' end and contain a region not found within type 2 messages. Type 1 mRNAs are present in endothelial cells (EC), platelets, white blood cells and in the cell lines CMK, HeLa, K562, HOG and A549, while type 2 messages are limited to EC. Type 1 messages contain exons E1-E10 whereas type 2 messages usually contain exons E1a, 1c, part of E1 and E2-E10. The translation start site is localized in the 3' end of E1, common for both type 1 and type 2 messages. Expression of these messages is regulated by two alternative promoters, P1 and P2. P1 is a TATA-less promoter containing an initiator element, multiple transcription start sites, several GC and CCAAT boxes, and GATA, NF-kappaB and ets consensus sequences. The cloned P1 drives efficient expression of the luciferase reporter gene. A high level of similarity between human P1 and its rat and mouse counterparts was observed. Promoter P2, located upstream of P1, contains a TATA box, GC boxes, a CCAAT box and GATA and ets consensus sequences. 3' RACE provided evidence for variability in the 3' UTR due to the presence of two polyadenylation signals. The finding of multiple regulatory sites in the promoters supplements the biochemical evidence that the F11R has several different roles in the functional repertoire of endothelial cells, platelets and other cells. In particular, the presence of NF-kappaB provides additional evidence to the significance of the F11R function in the initiation of inflammatory thrombosis.
F11受体（F11R）（又称JAM-1、JAM-A、CD321）是免疫球蛋白超家族的一种细胞粘附分子，参与血小板的粘附、分泌和聚集。此外，F11R在内皮细胞功能以及血小板与炎症内皮的粘附中起关键作用。在本研究中，我们利用人类F11R基因的部分序列、F11R cDNA以及未注释的人类基因组数据库中的信息来描绘F11R基因。我们发现F11R基因由13个外显子（E1a、1b、1c、E1 - E10）组成，这些外显子编码两组mRNA，它们在5'非翻译区（UTR）的长度和序列不同，分别称为1型和2型信息。1型cDNA在5'端较短，包含一个2型信息中未发现的区域。1型mRNA存在于内皮细胞（EC）、血小板、白细胞以及细胞系CMK、HeLa、K562、HOG和A549中，而2型信息仅限于EC。1型信息包含外显子E1 - E10，而2型信息通常包含外显子E1a、1c、部分E1和E2 - E10。翻译起始位点位于E1的3'端，1型和型2信息均如此。这些信息的表达受两个可变启动子P1和P2调控。P1是一个无TATA框的启动子，包含一个起始子元件、多个转录起始位点、几个GC盒和CCAAT盒，以及GATA、NF-κB和ets共有序列。克隆的P1能驱动荧光素酶报告基因的高效表达。观察到人类P1与其大鼠和小鼠对应物之间具有高度相似性。位于P1上游的启动子P2包含一个TATA框、GC盒、一个CCAAT盒以及GATA和ets共有序列。3'端快速扩增cDNA末端（3' RACE）证明由于存在两个聚腺苷酸化信号，3' UTR存在变异性。启动子中多个调控位点的发现补充了生化证据，即F11R在内皮细胞、血小板和其他细胞的功能库中具有多种不同作用。特别是，NF-κB的存在为F11R功能在炎症性血栓形成起始中的重要性提供了额外证据。
