High expression of membrane cofactor protein of complement (CD46) in human leukaemia cell lines: Implication of an alternatively spliced form containing the STA domain in CD46 up-regulation
High expression of membrane cofactor protein of complement (CD46) in human leukaemia cell lines: Implication of an alternatively spliced form containing the STA domain in CD46 up-regulation
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DOI：
10.1111/j.1365-3083.1995.tb03700.x
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发表时间：
1995-12-01
影响因子：
3.7
通讯作者：
Seya, T
中科院分区：
文献类型：
--
作者：
Hara, T;Suzuki, Y;Seya, T
人膜辅因子蛋白（MCP，CD 46）是麻疹病毒的受体，并作为补体调节剂，保护宿主细胞免受自体补体攻击。MCP是高度多态性的，由于多种mRNA剪接产物。T细胞系和骨髓细胞系的MCP表达水平通常比正常细胞系高2 - 8倍，而伯基特淋巴瘤B细胞系表达的MCP比不携带EB病毒的B细胞系少。该分子具有与功能结构域相邻的富含Ser/Thr（ST）的结构域，即短共有重复序列（SCR）。ST结构域和胞质尾区（CYT）有助于MCP多态性。ST结构域由三个外显子（A、B和C）编码，并且主要ST同种型是STABC、STBC和STC。作者通过使用STA和STC特异性抗体的流式细胞术、使用每个剪接变体的大小标记的逆转录-聚合酶链反应（RT-PCR）和使用STA特异性探针的RT-PCR/Southern印迹法，研究了MCP表达水平和亚型使用之间的关系。结果表明：（1）流式细胞术检测髓系和T细胞系的平均位移曲线为STC < STA，而B细胞系和正常血细胞的平均位移曲线为STA < STC;（2）RT-PCR检测的所有细胞系均表达STBC/CYT 1、STC/CYT 1、STBC/CYT 2和STC/CYT 2亚型的信息。STABC/CYT 2的条带与STC/CYT 1的条带重叠，并且STABC/CYT 1的条带在所检查的所有细胞系中是边缘的;（3）通过Southern印迹法对STABC同种型的半定量分析表明，与B淋巴细胞和正常白细胞相比，在髓系和T细胞系中存在高水平的STABC信息。因此，MCP的表达量与STABC信息水平平行，STABC信息水平在T细胞和髓系白血病细胞系中上调。
Human membrane cofactor protein (MCP, CD46) is a receptor for the measles virus and serves as a complement regulator which protects host cells from autologous complement attack. MCP is highly polymorphic due to a variety of mRNA splice products. The levels of MCP expression on T and myeloid cell lines are usually two-eightfold higher than those on their normal counterparts, whereas Burkitt's lymphoma B cell lines express less MCP than B cell lineages carrying no EB virus. The molecule has a Ser/Thr-rich (ST) domain adjacent to the functional domain, namely short consensus repeats (SCR). The ST domain and a cytoplasmic tail (CYT) contribute to the MCP polymorphism. The ST domain is encoded by three exons (A, B and C) and major ST isoforms are STABC, STBC and STC. The authors investigated the relationship between the expression levels and isoform usage of MCP by flow cytometry using specific antibodies against STA and STC, by reverse transcriptase-polymerase chain reaction (RT-PCR) with size markers for each splice variant, and by RT-PCR/Southern blotting using a specific probe for STA. The results were (1) the profiles of mean shifts of myeloid and T cell lines were STC < STA on flow cytometry while those of B cell lines and normal blood cells were STA < STC; (2) all cell lines tested by RT-PCR expressed the messages for the isoforms STBC/CYT1, STC/CYT1, STBC/CYT2, and STC/CYT2. The band for STABC/CYT2 overlapped that for STC/CYT1, and the band for STABC/CYT1 was marginal in all cell lines examined; (3) semi-quantitative analysis of the STABC isoforms by Southern blotting indicated the presence of high levels of the STABC messages in myeloid and T-cell lines in comparison with B lymphoid cells and normal leucocytes. Thus, the quantity of MCP expressed parallels the STABC message level, which is up-regulated in T and myeloid leukaemia cell lines.