Cell surface antigen CD109 is a novel member of the α2 macroglobulin/C3, C4, C5 family of thioester-containing proteins

被引:149
作者
Lin, M
Sutherland, R
Horsfall, W
Totty, N
Yeo, E
Nayar, R
Wu, XF
Schuh, AC
机构
[1] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A8, Canada
[2] Univ Toronto, Dept Med, Toronto, ON M5S 1A8, Canada
[3] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada
[4] Princess Margaret Hosp, Div Hematol Med Oncol, Toronto, ON, Canada
[5] Imperial Canc Res Fund, London, England
关键词
D O I
10.1182/blood.V99.5.1683
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Cell surface antigen CD109 is a glycosylphosphatidylinositol (GPl)-linked glycoprotein of approximately 170 kd found on a subset of hematopoietic stem and progenitor cells and on activated platelets and T cells. Although it has been suggested that T-cell CD109 may play a role In antibody-inducing T-helper function and it is known that platelet CD109 carries the Gov alloantigen system, the role of CD109 in hematopoletic cells remains largely unknown. As a first step toward elucidating the function of CD109, we have Isolated and characterized a human CD109 cDNA from KG1a and endothelial cells. The isolated cDNA comprises a 4335 bp open-reading frame encoding a 1445 amino acid (aa) protein of approximately 162 kd that contains a 21 aa N-terminal leader peptide, 17 potential N-linked glycosylation sites, and a C-terminal GPl anchor cleavage-addition site. We report that CD109 is a novel member of the alpha2 macroglobulin (alpha2M)/C3, C4, C5 family of thioester-containing proteins, and we demonstrate that native CD109 does indeed contain an intact thioester. Analysis of the CD109 aa sequence suggests that CD109 is likely activated by proteolytic cleavage and thereby becomes capable of thioester-mediated covalent binding to adjacent molecules or cells. In addition, the predicted chemical reactivity of the activated CD109 thioester is complement like rather than resembling that of alpha2M proteins. Thus, not only is CD109 potentially capable of covalent binding to carbohydrate and protein targets, but the t(1/2), of its activated thioester is likely extremely short, indicating that CD109 action is highly restricted spatially to the site of its activation.
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页码:1683 / 1691
页数:9
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