Rt. Plott et al., PEMPHIGUS-VULGARIS ANTIGEN LACKS BIOCHEMICAL-PROPERTIES CHARACTERISTIC OF CLASSICAL CADHERINS, Journal of investigative dermatology, 103(2), 1994, pp. 168-172
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.