A pathogenic autoantibody, pemphigus vulgaris-IgG, induces phosphorylation of desmoglein 3, and its dissociation from plakoglobin in cultured keratinocytes.
Pemphigus vulgaris (PV) is an autoimmune blistering skin disease, which is characterized by autoantibodies to a specific desmosomal constituent, i.e. desmoglein 3 (Dsg3). In this study, we analyzed phosphorylation of desmosomal proteins and their molecular interactions after PV-IgG binding to Dsg3 using DJM-1 cells, a squamous cell carcinoma cell line, and normal human keratinocytes. Cells were metabolically labeled with 32P inorganic phosphate, followed by stimulation with the IgG fractions from five PV patients or normal individuals for 20 min. Phosphorylation of specific desmosomal components and their molecular interactions were studied in immunoprecipitates using PV-IgG and anti-plakoglobin (PG) antibodies. PV-IgG binding alone induced the phosphorylation of Dsg3 at serine residues. Although Dsg3 and PG were coprecipitated by PV-IgG-immunoprecipitation when treated with normal IgG, PG was not coprecipitated with Dsg3 when stimulated with PV-IgG, suggesting that PV-IgG binding to Dsg3 caused the dissociation of Dsg3 from PG. These results demonstrate that the binding of pathogenic PV autoantibodies to the cell surface antigen Dsg3, which is an adhesion molecule categorized into desmosomal cadherins, caused particular phosphorylation of Dsg3 and its dissociation from PG.
Aoyama
Y
Y
Department of Dermatology, Gifu University School of Medicine, Gifu City, Japan. ymaoyama@gumail.cc.gifu-u.ac.jp
Owada
M K
MK
Kitajima
Y
Y
D001323:Autoantibodies / Q000378:metabolism*; D001324:Autoantigens / Q000737:chemistry / Q000378:metabolism*; D015820:Cadherins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D051184:Desmoglein 3; D051182:Desmogleins; D051180:Desmoplakins; D003896:Desmosomes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D010392:Pemphigus / Q000276:immunology*; D010766:Phosphorylation; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D051185:gamma Catenin
D001323:Autoantibodies; D001324:Autoantigens; D015820:Cadherins; D003598:Cytoskeletal Proteins; C071894:DSG3 protein, human; D051184:Desmoglein 3; D051182:Desmogleins; D051180:Desmoplakins; D007074:Immunoglobulin G; D051185:gamma Catenin; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate