title: Epithelial membrane glycoprotein PAS-IV is related to platelet glycoprotein IIIb binding to thrombospondin but not to malaria-infected erythrocytes.
abstract: Glycoprotein (GP) IIIb (also termed GPIV or CD36) is an integral platelet membrane protein, and has been identified as a binding site for thrombospondin, collagen, and malaria-infected erythrocytes. PAS-IV is an integral membrane protein found in lactating mammary epithelial cells and capillary endothelial cells. The N-terminal sequence of PAS-IV is nearly identical to that of GPIIIb and monospecific anti-PAS-IV antibody reacts with GPIIIb, indicating that PAS-IV is structurally related to GPIIIb. In this study, human platelet GPIIIb and bovine epithelial PAS-IV were compared in terms of structural, immunologic, and functional characteristics. The two-dimensional tryptic peptide map of both intact and deglycosylated PAS-IV was highly similar but not identical to that of GPIIIb. PAS-IV and GPIIIb reacted to an equal extent with monoclonal antibodies OKM5 and OKM8 by enzyme-linked immunosorbent assay. GPIIIb bound to surface immobilized thrombospondin (TSP) in a concentration-dependent and saturable manner, with approximately 60% reduction in binding in the presence of EDTA. PAS-IV bound to TSP with similar characteristics except that maximum binding was consistently approximately 50% of that of GPIIIb and binding was not inhibited by EDTA. GPIIIb supported adhesion of Plasmodium falciparum-infected erythrocytes (PRBC) in a dose-dependent manner while no significant adhesion of PRBC to PAS-IV was observed. Our data demonstrate that while epithelial PAS-IV and platelet GPIIIb are structurally and immunologically related, there are significant differences in their functional properties. Whether this result is due to different posttranslational glycosylation modifications or that PAS-IV and GPIIIb represent a family of related cell adhesive protein receptors remains to be determined.
authors.affiliation: Department of Medicine, Stanford University Medical School, CA 94305-5112.
authors.forename: B
authors.initials: B
authors.lastname: Catimel
authors.forename: J L
authors.initials: JL
authors.lastname: McGregor
authors.forename: T
authors.initials: T
authors.lastname: Hasler
authors.forename: D E
authors.initials: DE
authors.lastname: Greenwalt
authors.forename: R J
authors.initials: RJ
authors.lastname: Howard
authors.forename: L L
authors.initials: LL
authors.lastname: Leung
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018955:CD36 Antigens; D002417:Cattle; D004848:Epithelium / Q000737:chemistry; D000939:Epitopes / Q000276:immunology; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D006031:Glycosylation; D006801:Humans; D008288:Malaria / Q000097:blood*; D008321:Mammary Glands, Animal / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry; D010449:Peptide Mapping; D010963:Plasmodium falciparum; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D019699:Thrombospondins; D014357:Trypsin
chemical_list: D000911:Antibodies, Monoclonal; D018955:CD36 Antigens; D000939:Epitopes; D008562:Membrane Glycoproteins; C069283:PAS-4 protein, Bos taurus; D010446:Peptide Fragments; D010980:Platelet Membrane Glycoproteins; D019699:Thrombospondins; D014357:Trypsin