Human lymphocytes interact directly with CD47 through a novel member of the signal regulatory protein (SIRP) family
Human lymphocytes interact directly with CD47 through a novel member of the signal regulatory protein (SIRP) family
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DOI：
10.4049/jimmunol.173.4.2562
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发表时间：
2004-08-15
影响因子：
4.4
通讯作者：
Barclay, AN
中科院分区：
文献类型：
--
作者：
Brooke, G;Holbrook, JD;Barclay, AN
两种密切相关的蛋白，信号调节蛋白α (SIRPalpha; SHPS-1/CD172)和SIRFbeta，已经在人类中被发现。第三个SIRP蛋白的存在仅由cDNA序列推断。我们发现这第三个SIRP是一个独立的基因，表达为与α和β基因具有独特特征的蛋白质，并建议将该基因命名为SIRPgamma。我们已经将SIRPgamma的细胞外区域表达为可溶性蛋白，并表明，与SIRPa一样，它与CD47结合，但与SIRPalpha （K-d，类似于23mum）相比，其亲和力较低（K-d，类似于23mum）。SIRPgamma特异性单克隆抗体显示，与sirppha和- β不同，它在髓细胞上不表达，而是在大多数T细胞和一部分B细胞上表达。SIRPgamma的短细胞质尾部不包含任何已知的信号基序，也不像SIRPbeta那样包含DAP12相互作用所需的特征赖氨酸。DAP12共表达是SIRPbeta表面表达的必要条件，而SIRPgamma在其缺失的情况下表达。因此，sirgamma -CD47相互作用可能不像SIRPalpha-CD47那样具有双向信号，而是仅通过CD47使用单向信号。
Two closely related proteins, signal regulatory protein alpha (SIRPalpha; SHPS-1/CD172) and SIRFbeta, have been described in humans. The existence of a third SIRP protein has been suggested by cDNA sequence only. We show that this third SIRP is a separate gene that is expressed as a protein with unique characteristics from both alpha and beta genes and suggest that this gene should be termed SIRPgamma. We have expressed the extracellular region of SIRPgamma as a soluble protein and have shown that, like SIRPa, it binds CD47, but with a lower affinity (K-d, similar to23 muM) compared with SIRPalpha (K-d, similar to2 muM). mAbs specific to SIRPgamma show that it was not expressed on myeloid cells, in contrast to SIRPalpha and -beta, being expressed instead on the majority of T cells and a proportion of B cells. The short cytoplasmic tail of SIRPgamma does not contain any known signaling motifs, nor does it contain a characteristic lysine, as with SIRPbeta, that is required for DAP12 interaction. DAP12 coexpression is a requirement for SIRPbeta surface expression, whereas SIRPgamma is expressed in its absence. The SIRPgamma-CD47 interaction may therefore not be capable of bidirectional signaling as with the SIRPalpha-CD47, but, instead, use unidirectional signaling via CD47 only.