Rh-related antigen CD47 is the signal-transducer integrin-associated protein.
Integrin-associated protein (IAP) is a 50-kDa membrane protein with an amino-terminal immunoglobulin domain and a carboxyl-terminal multiply membrane-spanning region. It is physically and functionally associated with the integrin alpha v beta 3 vitronectin receptor and is involved in the increase in intracellular calcium concentration, which occurs upon cell adhesion to extracellular matrix. Oxidative burst in neutrophils can be induced or inhibited via IAP. Surprisingly, IAP is also expressed on erythrocytes, which have no known integrins. IAP has been shown to be identical to OA3, an ovarian carcinoma antigen. We now show that IAP expression is reduced on Rhnull erythrocytes. The IAP structural gene is mapped to q13.1-2 on human chromosome 3, within a region known to contain a gene encoding the Rh-associated 1D8 antigen. By expression studies on human erythrocytes and IAP transfectants, IAP is shown to be identical to the 1D8 antigen and to CD47, a cell surface protein with broad tissue distribution, reduced in expression on Rhnull erythrocytes. Two CD47 antibodies recognize the immunoglobulin domain of IAP, as does antibody 1D8. These studies suggest the possibility that IAP and the Rh polypeptides may share a pathway for membrane expression on erythrocytes. Furthermore, decreased expression of IAP on Rhnull cells may contribute to the these cells' abnormal cation permeabilities. These studies demonstrate an unexpected link between integrin signal transduction and erythrocyte membrane structure.
Lindberg
F P
FP
Department of Medicine, University School of Medicine, St. Louis, Missouri 63110.
Lublin
D M
DM
Telen
M J
MJ
Veile
R A
RA
Miller
Y E
YE
Donis-Keller
H
H
Brown
E J
EJ
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D015153:Blotting, Western; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D004910:Erythrocyte Membrane / Q000276:immunology / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D005796:Genes; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D009036:Moths; D011994:Recombinant Proteins / Q000032:analysis / Q000276:immunology; D012204:Rh-Hr Blood-Group System / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014162:Transfection
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; C497895:Cd47 protein, mouse; D011994:Recombinant Proteins; D012204:Rh-Hr Blood-Group System