Cloning of glycoprotein D cDNA, which encodes the major subunit of the Duffy blood group system and the receptor for the Plasmodium vivax malaria parasite.

Chaudhuri, Asok; Polyakova, J.; Zbrzezna, Valerie; Williams, Kelly P.; Gulati, Sunita; Pogo, A.O.

doi:10.1073/pnas.90.22.10793

Cited by 227 publications

(163 citation statements)

References 27 publications

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“…Therefore, we explored the possibility of using a type I transmembrane protein in the construction of RhD fusion proteins. Fy protein, a blood group antigen and a promiscuous chemokine receptor, has been expressed on the surface of K562 cells that does not have detectable background (18,20). The extracellularly located N-terminal domain (64 residues) of the protein is recognized by anti-Fy6.…”

Section: Discussionmentioning

confidence: 99%

Use of RhD Fusion Protein Expressed on K562 Cell Surface in the Study of Molecular Basis for D Antigenic Epitopes

Zhu¹,

Haller²,

Li³

et al. 1999

Journal of Biological Chemistry

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The human D antigens, one of the most clinically important blood groups, are presented by RhD protein with a putative 12 transmembrane topology. To understand the molecular basis for the complex antigenic profile of RhD protein, we expressed a series of RhD fusion proteins using different portions of Duffy protein as a tag in erythroleukemic K562 cells. Because the reactivity of monoclonal anti-RhD antibody, LOR15C9, depends mainly on the sequence coded by exon 7 of RhD, we altered DNA sequence corresponding to the amino acid residues 323-331(A) and 350 -354(B) in the exon 7. The mutation in region B resulted in a severe reduction in LOR15C9 binding by flow cytometry analysis, suggesting that region B may play an important role in constituting antigen epitopes recognized by LOR15C9. On the other hand, a slight decrease in the antibody binding was observed for the region A mutant, suggesting that the intracellularly located region A may elicit a long distance effect on the formation of exofacial antigen epitopes. In addition, using various monoclonal antibodies against RhD, we compared the antigenic profile of expressed RhD fusion protein with that of endogenous RhD in K562 cells as well as in erythrocytes.As one of the most important blood group systems involved in blood transfusion and hemolytic disease, the Rh antigens are present on the erythrocyte surface as a complex including Rh30 proteins (RhD and RhCE) and Rh50 glycoprotein (see recent reviews in Refs. 1 and 2). Hartel-Schenk and Agre (3) first demonstrated that the Rh polypeptides migrated through sucrose gradients as a complex with an apparent M r of 170,000. Based on proteolytic digestion and immunoblotting, Eyers et al. (4) proposed a model that consists of two of each Rh30 and Rh50 molecules, with their N-terminal portions forming the core of the complex. The genes encoding RhD and RhCE are located at chromosome 1p34-p36 (5), whereas RH50 gene is at chromosome 6p11-21 (6). These three genes share not only a similar exon-intron composition but also homology in their deduced amino acid sequences (92% identity between RhD and RhCE, and 36% identity between Rh30 and Rh50) (2). Therefore, it appears that all three of these molecules belong to a family of structurally related membrane proteins.The multiprotein complex provides the basis for enormously complicated D antigenic epitopes, which have been serologically classified into nine epitopes, epD1 to epD9 (7). Most of the information regarding the molecular basis for D epitopes has been derived from genetic analysis of RhD variants where part of the RhD gene is missing or replaced by the highly homologous RhCE sequence (2). Thus, D VI phenotype, characterized as lack of epD1, 2, 5, 6, 7, and 8, contains rearranged RHD gene where its exons 4 -6 are replaced with RHCE equivalents (8). In D IVa phenotype that lacks epD 1, 2, 3, and 9, there is a rearrangement of exon 3 and part of exon 7 of the RHD gene (9). These observations suggest that serologically defined D epitopes are organized into overlapping m...

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Section: Discussionmentioning

confidence: 99%

Use of RhD Fusion Protein Expressed on K562 Cell Surface in the Study of Molecular Basis for D Antigenic Epitopes

Zhu¹,

Haller²,

Li³

et al. 1999

Journal of Biological Chemistry

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“…However, we did not find any significant difference in the proliferation and invasion potential, comparing the DARC-transfected cells with the mocktranfected cells or wild-type MDA-MB-435HM, which indicating that the enhanced expression of DARC had no remarkable influence on the intracellular signaling pathway associated with the tumor cells proliferation and invasion in vitro. It has been reported that DARC gene modification has no influence in cell growth characteristics in vitro, except for their acquired chemokine-binding capacity in human erythroleukemic cell line K562 (Chaudhuri et al, 1994) as well as in human pulmonary cancer cell A549 (Addison et al, 2004). DARC gene expression appears to effect in vivo growth and has no effect on in vitro growth.…”

Section: Inhibition Of Breast Cancer Growth and Metastasis By Darcmentioning

confidence: 99%

Enhanced expression of Duffy antigen receptor for chemokines by breast cancer cells attenuates growth and metastasis potential

et al. 2006

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In addition to the role in regulating leukocyte trafficking, chemokines recently have been shown to be involved in cancer growth and metastasis. Chemokine network in tumor neovascularity may be regulated by decoy receptors. Duffy antigen receptor for chemokines (DARC) is a specific decoy receptor binding with the angiogenic CC and CXC chemokines. To investigate the effects of DARC on the tumorigenesis and the metastasis potential of human breast cancer cells, human DARC cDNA was reintroduced into the MDA-MB-231 and MDA-MB-435HM cells which have a high capability of spontaneous pulmonary metastasis. We demonstrated that DARC overexpression induced inhibition of tumorigenesis and/ or metastasis through interfering with the tumor angiogenesis in vivo. This inhibition is associated with decreasing CCL2 protein levels, and MVD and MMP-9 expression in xenograft tumors. In human breast cancer samples, we also demonstrated that low expression of the DARC protein is significantly associated with estrogen receptor (ER) status, MVD, lymph node metastasis, distant metastasis and poor survival. Our results suggest for the first time that DARC is a negative regulator of growth in breast cancer, mainly by sequestration of angiogenic chemokines and subsequent inhibition of tumor neovascularity.

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“…Another possible IL-8 receptor, the Duffy antigen, was originally identified as a blood group antigen required for invasion by the malarial parasites, Plasmodium vivax and Plasmodium knowlesi (71)(72)(73). Further studies revealed that a chemokinebinding protein expressed on red blood cells is identical to the Duffy antigen, which was subsequently renamed Duffy antigen receptor for chemokines (DARC) (74).…”

Section: Fig 5 Il-8 Is a Potent Chemoattractant For Himec Migrationmentioning

confidence: 99%

Angiogenic Effects of Interleukin 8 (CXCL8) in Human Intestinal Microvascular Endothelial Cells Are Mediated by CXCR2

Heidemann¹,

Ogawa²,

Dwinell³

et al. 2003

Journal of Biological Chemistry

431

321

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Cloning of glycoprotein D cDNA, which encodes the major subunit of the Duffy blood group system and the receptor for the Plasmodium vivax malaria parasite.

Cited by 227 publications

References 27 publications

Use of RhD Fusion Protein Expressed on K562 Cell Surface in the Study of Molecular Basis for D Antigenic Epitopes

Use of RhD Fusion Protein Expressed on K562 Cell Surface in the Study of Molecular Basis for D Antigenic Epitopes

Enhanced expression of Duffy antigen receptor for chemokines by breast cancer cells attenuates growth and metastasis potential

Angiogenic Effects of Interleukin 8 (CXCL8) in Human Intestinal Microvascular Endothelial Cells Are Mediated by CXCR2

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