Pemphigus vulgaris antigen lacks biochemical properties characteristic of classical cadherins.
Pemphigus vulgaris antigen (PVA) is a member of the desmoglein subfamily of the cadherin supergene family. PVA has homology to the classical cadherins (e.g., E-cadherin), both in its extracellular and cytoplasmic domains. Classical cadherins possess certain well-defined and characteristic biochemical properties of both domains. The cytoplasmic domain binds alpha-, beta-, and gamma-catenins. The extracellular domain is protected by calcium from degradation by trypsin. In this study we show that PVA does not share these characteristic biochemical features. Immunoprecipitation of E-cadherin and PVA from human keratinocytes shows that under the same conditions in which the catenins co-precipitate with E-cadherin, only plakoglobin (which co-migrates with gamma-catenin) co-precipitates with PVA. Treatment of keratinocytes with 0.01% trypsin in 1 mM calcium (T/C) does not degrade the extracellular region of E-cadherin, but does partially degrade that of PVA. This increased T/C susceptibility of PVA is not due to its cytoplasmic domain, as the same sensitivity of the extracellular domain of PVA to T/C was observed in L cell clones transfected with a chimeric cDNA that encoded for the extracellular domain of PVA and the cytoplasmic domain of E-cadherin. These data demonstrate that although the desmogleins and classical cadherins share striking amino acid homologies in both the cytoplasmic and extracellular domains, they do not exhibit identical biochemical properties and, by extension, may not subserve identical cell biologic functions.
Dermatology Branch, National Institutes of Health, Bethesda, Maryland 20892.
R T
RT
Plott
M
M
Amagai
M C
MC
Udey
J R
JR
Stanley
D000595:Amino Acid Sequence; D001324:Autoantigens / Q000737:chemistry; D015820:Cadherins / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects / Q000276:immunology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051184:Desmoglein 3; D005110:Extracellular Space / Q000187:drug effects / Q000276:immunology; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008969:Molecular Sequence Data; D010392:Pemphigus / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D014357:Trypsin / Q000494:pharmacology; D051178:alpha Catenin; D051176:beta Catenin
D001324:Autoantigens; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; C071894:DSG3 protein, human; D051184:Desmoglein 3; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D014357:Trypsin; D002122:Calcium Chloride