Fraser Christopher C, Howie Duncan, Morra Massimo, Qiu Yubin, Murphy Curran, Shen Qiong, Gutierrez-Ramos Jose-Carlos, Coyle Anthony, Kingsbury Gillian A, Terhorst Cox
Millennium Pharmaceuticals, 75 Sidney Street, Cambridge, MA 02139, USA.
Immunogenetics. 2002 Feb;53(10-11):843-50. doi: 10.1007/s00251-001-0415-7. Epub 2002 Jan 23.
The SLAM family of human genes currently consists of seven related members of the immunoglobulin superfamily, membrane-associated proteins, including CD150 (SLAM), CD244 (2B4), CD84, CD229 ( Ly-9), BLAME, CD48, and 19A. These genes are expressed to varying degrees in subsets of immune cells (T, B, natural killer, and myeloid cells) and may function as ligands or receptors. This set of genes, related to CD2 and CD58 on Chromosome (Chr) 1p98, are found clustered close together in the human genome on Chr 1q22. Four of these family members (CD150, CD244, CD84, CD229) contain conserved tyrosine motifs in their cytoplasmic tails that enable them to bind intracellular signaling molecules SAP and EAT-2. SAP is mutated in human X-linked lymphoproliferative disease (XLP), and studies in XLP patients have shown that improper signaling via molecules that bind SAP contributes to the disease. We have identified two new members of the SLAM family (SF), which we term SF2000 and SF2001, which are expressed in immune cells and map in the SLAM gene cluster. SF2001 does not contain SAP-binding motifs in its short cytoplasmic tail. SF2000, which is co-expressed with SAP in T cells, binds both SAP and EAT-2. The data suggest that signaling through SF2000, together with CD150, CD244, CD84, and CD229, is controlled by SAP and therefore contributes to the pathogenesis of XLP.
人类基因的信号淋巴细胞激活分子（SLAM）家族目前由免疫球蛋白超家族的七个相关成员组成，这些成员均为膜相关蛋白，包括CD150（SLAM）、CD244（2B4）、CD84、CD229（Ly-9）、BLAME、CD48和19A。这些基因在免疫细胞亚群（T细胞、B细胞、自然杀伤细胞和髓样细胞）中表达程度各异，可能作为配体或受体发挥作用。这组与1号染色体（Chr）1p98上的CD2和CD58相关的基因，在人类基因组中位于1q22，紧密聚集在一起。这些家族成员中的四个（CD150、CD244、CD84、CD229）在其胞质尾部含有保守的酪氨酸基序，使其能够结合细胞内信号分子SAP和EAT-2。SAP在人类X连锁淋巴增殖性疾病（XLP）中发生突变，对XLP患者的研究表明，通过与SAP结合的分子进行的不当信号传导会导致该疾病。我们鉴定出了信号淋巴细胞激活分子家族（SF）的两个新成员，我们将其命名为SF2000和SF2001，它们在免疫细胞中表达，并定位于信号淋巴细胞激活分子基因簇。SF2001在其短胞质尾部不包含SAP结合基序。在T细胞中与SAP共表达的SF2000既能结合SAP也能结合EAT-2。数据表明，通过SF2000以及CD150、CD244、CD84和CD229进行的信号传导受SAP控制，因此促成了XLP的发病机制。
