Cellular Expression of a GPI-Linked T Cell Activation Protein

Haregewoin, Abebe; Solomon, Keith R.; Hom, Richard C.; Soman, Gopalan; Bergelson, Jeffrey M.; Bhan, Atul K.; Finberg, Robert W.

doi:10.1006/cimm.1994.1181

Cited by 45 publications

(46 citation statements)

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“…Echoviruses 1 (Farouk), 6 (D'Amori), 7 (Wallace), 8 (Bryson), 11 (Gregory), 12 (Travis 2-85), 20 (JV-1), and 21 (Farina) were obtained from the American Type Culture Collection and grown in HeLa cells. Antibody inhibition ofviral cytopathic effect and inhibition of plaque formation were measured as described (2).…”

Section: Methodsmentioning

confidence: 99%

Decay-accelerating factor (CD55), a glycosylphosphatidylinositol-anchored complement regulatory protein, is a receptor for several echoviruses.

Bergelson

Chan

Solomon

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

302

199

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Echoviruses are human pathogens belonging to the picornavirus family. Decay-accelerating factor (DAF) is a glycosylphosphatidylhinostol (GPI)-anchored surface protein that protects cells from lysis by autologous complement. Anti-DAF monoclonal antibodies prevented echovirus 7 attachment to susceptible cells and protected cells from infection. HeLa cells specifically lost the capacity to bind echovirus 7 when treated with phosphatidylinositol-specific phospholipase C, an enzyme that releases GPI-anchored proteins from the cell surface, indicating that the virus receptor, like DAF, is a GPI-anchored protein. Although Chinese hamster ovary cells do not bind echovirus 7, transfectants expressing human DAF bound virus efficiently, and binding was prevented by pretreatment with an anti-DAF monoclonal antibody. Anti-DAF antibodies prevented infection by at least six echovirus seroypes. These results indicate that DAF is the receptor mediating attachment and infection by several echoviruses.

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Section: Methodsmentioning

confidence: 99%

Decay-accelerating factor (CD55), a glycosylphosphatidylinositol-anchored complement regulatory protein, is a receptor for several echoviruses.

Bergelson

Chan

Solomon

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

302

199

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“…Indeed, mutations in TGF-b receptors or in downstream signaling molecules have been associated with the development of colorectal and pancreatic cancers (Xu et al, 2000;Jakowlew, 2006). CD109 is a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein and is a member of the a2-macroglobulin (a2 M) -C3, C4 and C5 family (Sutherland et al, 1991;Haregewoin et al, 1994;Lin et al, 2002). CD109 was first identified as a cell-surface antigen, detected in the lymphoid/myeloid cell line KG1a (Sutherland et al, 1991).…”

Section: Kip1mentioning

confidence: 99%

Processing of CD109 by furin and its role in the regulation of TGF-β signaling

et al. 2010

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CD109 is a glycosylphosphatidylinositol (GPI)-anchored glycoprotein, whose expression is upregulated in squamous cell carcinomas of the lung, esophagus, uterus and oral cavity. CD109 negatively regulates transforming growth factor (TGF)-b signaling in keratinocytes by directly modulating receptor activity. In this study, we further characterized CD109 regulation of TGF-b signaling and cell proliferation. We found that CD109 is produced as a 205 kDa glycoprotein, which is then processed in the Golgi apparatus into 180 kDa and 25 kDa proteins by furin (furinase). 180 kDa CD109 associated with GPI-anchored 25 kDa CD109 on the cell surface and was also secreted into the culture medium. To investigate whether furinase cleavage of CD109 is necessary for its biological activity, we mutated arginine 1273 in the CD109 furinase cleavage motif (amino acid 1270-RRRR-1273) to serine (R1273S). Interestingly, CD109 R1273S neither significantly impaired TGF-b signaling nor affected TGF-b-mediated suppression of cell growth, although it was expressed on the cell surface as a 205 kDa protein. Consistent with this finding, the 180 kDa and 25 kDa CD109 complex, but not CD109 R1273S, associated with the type I TGF-b receptor. These findings indicate that processing of CD109 into 180 kDa and 25 kDa proteins by furin, followed by complex formation with the type I TGF-b receptor is required for the regulation of TGF-b signaling in cancer cells and keratinocytes.

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“…6 Antibodies to CD109 recognize monomeric polypeptides of about 170 kd and 150 kd in lysates of KG1a cells, T-cell lines, and activated T lymphoblasts, endothelial cells, and activated platelets. 3,[7][8][9][10][11] Peptide mapping and amino acid (aa) analysis indicate that the 150-kd form is likely derived proteolytically from the 170-kd form. 3,10 An additional band of about 120 kd that is occasionally observed arises through calcium-dependent proteolysis of the larger forms.…”

Section: Introductionmentioning

confidence: 99%

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

Lin

Sutherland

Horsfall

et al. 2002

Blood

171

163

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Cell surface antigen CD109 is a glycosylphosphatidylinositol (GPI)-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 antibodyinducing T-helper function and it is known that platelet CD109 carries the Gov alloantigen system, the role of CD109 in hematopoietic 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 Nterminal leader peptide, 17 potential Nlinked glycosylation sites, and a C-terminal GPI anchor cleavage-addition site. We report that CD109 is a novel member of the ␣2 macroglobulin (␣2M)/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 complementlike rather than resembling that of ␣2M proteins. Thus, not only is CD109 potentially capable of covalent binding to carbohydrate and protein targets, but the t ½ of its activated thioester is likely extremely short, indicating that CD109 action is highly restricted spatially to the site of its activation. IntroductionTo identify new surface antigens expressed by primitive hematopoietic stem and progenitor cells, we raised a series of monoclonal antibodies (mAbs) against the primitive CD34 ϩ acute myeloid leukemia cell line, KG1a. 1-3 Four of these mAbs-8A3, 7D1, 8A1, and 7C5-recognized a novel glycoprotein of approximately 170 kd that was expressed in a restricted pattern in the hematopoietic compartment and by endothelial cells. 4 Subsequently found to be identified by a number of additional mAbs, this antigen was designated CDw109 in 1993 5 and CD109 in 1996. 6 Antibodies to CD109 recognize monomeric polypeptides of about 170 kd and 150 kd in lysates of KG1a cells, T-cell lines, and activated T lymphoblasts, endothelial cells, and activated platelets. 3,[7][8][9][10][11] Peptide mapping and amino acid (aa) analysis indicate that the 150-kd form is likely derived proteolytically from the 170-kd form. 3,10 An additional band of about 120 kd that is occasionally observed arises through calcium-dependent proteolysis of the larger forms. 3,10 CD109 contains several N-linked endoglycosidase H-sensitive hybrid-type glycans but no O-linked glycans. 3,10 Consistent with this finding, ABH blood group antigens have recently been shown to be carried by platelet CD109. 12 KG1a CD109 is susceptible to cleavage with phosphatidylinositolspecific phospholipase C (PI-PLC), indicating that CD109 is bo...

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Cellular Expression of a GPI-Linked T Cell Activation Protein

Cited by 45 publications

References 0 publications

Decay-accelerating factor (CD55), a glycosylphosphatidylinositol-anchored complement regulatory protein, is a receptor for several echoviruses.

Decay-accelerating factor (CD55), a glycosylphosphatidylinositol-anchored complement regulatory protein, is a receptor for several echoviruses.

Processing of CD109 by furin and its role in the regulation of TGF-β signaling

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

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