title: Molecular identity and cellular distribution of advanced glycation endproduct receptors: relationship of p60 to OST-48 and p90 to 80K-H membrane proteins.
abstract: Advanced glycation endproducts (AGEs) are derivatives of nonenzymatic reactions between sugars and protein or lipids, and together with AGE-specific receptors are involved in numerous pathogenic processes associated with aging and hyperglycemia. Two of the known AGE-binding proteins isolated from rat liver membranes, p60 and p90, have been partially sequenced. We now report that the N-terminal sequence of p60 exhibits 95% identity to OST-48, a 48-kDa member of the oligosaccharyltransferase complex found in microsomal membranes, while sequence analysis of p90 revealed 73% and 85% identity to the N-terminal and internal sequences, respectively, of human 80K-H, a 80- to 87-kDa protein substrate for protein kinase C. AGE-ligand and Western analyses of purified oligosaccharyltransferase complex, enriched rough endoplasmic reticulum, smooth endoplasmic reticulum, and plasma membranes from rat liver or RAW 264.7 macrophages yielded a single protein of approximately 50 kDa recognized by both anti-p60 and anti-OST-48 antibodies, and also exhibited AGE-specific binding. Immunoprecipitated OST-48 from rat rough endoplasmic reticulum fractions exhibited both AGE binding and immunoreactivity to an anti-p60 antibody. Immune IgG raised to recombinant OST-48 and 80K-H inhibited binding of AGE-bovine serum albumin to cell membranes in a dose-dependent manner. Immunostaining and flow cytometry demonstrated the surface expression of OST-48 and 80K-H on numerous cell types and tissues, including mononuclear, endothelial, renal, and brain neuronal and glial cells. We conclude that the AGE receptor components p60 and p90 are identical to OST-48, and 80K-H, respectively, and that they together contribute to the processing of AGEs from extra- and intracellular compartments and in the cellular responses associated with these pathogenic substances.
authors.affiliation: Picower Institute for Medical Research, Manhasset, NY 11030, USA.
authors.forename: Y M
authors.initials: YM
authors.lastname: Li
authors.forename: T
authors.initials: T
authors.lastname: Mitsuhashi
authors.forename: D
authors.initials: D
authors.lastname: Wojciechowicz
authors.forename: N
authors.initials: N
authors.lastname: Shimizu
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: A
authors.initials: A
authors.lastname: Stitt
authors.forename: C
authors.initials: C
authors.lastname: He
authors.forename: D
authors.initials: D
authors.lastname: Banerjee
authors.forename: H
authors.initials: H
authors.lastname: Vlassara
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D018870:Endoplasmic Reticulum, Rough / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005959:Glucosidases; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006602:Hexosyltransferases; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D010750:Phosphoproteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014166:Transferases / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D017127:Glycation End Products, Advanced; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; C512949:Prkcsh protein, mouse; C512948:Prkcsh protein, rat; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D014166:Transferases; D006602:Hexosyltransferases; C025620:dolichyl-diphosphooligosaccharide - protein glycotransferase; D005959:Glucosidases; C070368:PRKCSH protein, human