PEMPHIGUS-VULGARIS ANTIGEN LACKS BIOCHEMICAL-PROPERTIES CHARACTERISTIC OF CLASSICAL CADHERINS

Pemphigus vulgaris antigen (PVA) is a member of the desmoglein subfami ly of the cadherin supergene family. PVA has homology to the classical cadherins (e.g., E-cadherin), both in its extracellular and cytoplasm ic domains. Classical cadherins possess certain well-defined and chara cteristic biochemical properties of both domains. The cytoplasmic doma in binds alpha-, beta-, and gamma-catenins. The extracellular domain i s protected by calcium from degradation by trypsin. In this study we s how that PVA does not share these characteristic biochemical features. Immunoprecipitation of E-cadherin and PVA from human keratinocytes sh ows that under the same conditions in which the catenins co-precipitat e with E-cadherin, only plakoglobin (which co-migrates with gamma-cate nin) co-precipitates with PVA. Treatment of keratinocytes with 0.01% t rypsin 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 th e same sensitivity of the extracellular domain of PVA to T/C was obser ved in L cell clones transfected with a chimeric cDNA that encoded for the extracellular domain of PVA and the cytoplasmic domain of E-cadhe rin. These data demonstrate that although the desmogleins and classica l cadherins share striking amino acid homologies in both the cytoplasm ic and extracellular domains, they do not exhibit identical biochemica l properties and, by extension, may not subserve identical cell biolog ic functions.