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J Biol Chem, Vol. 273, Issue 28, 17565-17572, July 10, 1998
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From Endothelial cells express two major cadherins,
VE- and N-cadherins, but only the former consistently participates in
adherens junction organization. In heart microvascular endothelial
cells, we identified a new member of the cadherin superfamily using
polymerase chain reaction. The entire putative coding sequence was
determined. Similarly to protocadherins, while the extracellular domain
presented homology with other members of the cadherin superfamily, the
intracellular region was unrelated either to cadherins or to any other
known protein. We propose for this new protein the name of vascular endothelial cadherin-2. By Northern blot analysis, the mRNA was present only in cultured endothelial cell lines but not in other cell
types such as NIH 3T3, Chinese hamster ovary, or L cells. In addition,
mRNA was particularly abundant in highly vascularized organs such
as lung or kidney. In endothelial cells and transfectants, this
cadherin was unable to bind catenins and presented a weak association
with the cytoskeleton. This new molecule shares some functional
properties with VE-cadherin and other members of the cadherin family.
In Chinese hamster ovary transfectants it promoted homotypic
Ca2+ dependent aggregation and adhesion and clustered
at intercellular junctions. However, in contrast to VE-cadherin, it did
not modify paracellular permeability, cell migration, and
density-dependent cell growth. These observations suggest
that different cadherins may promote homophilic cell-to-cell adhesion
but that the functional consequences of this interaction depend on
their binding to specific intracellular signaling/cytoskeletal
proteins.
Istituto di Ricerche Farmacologiche Mario Negri,
Via Eritrea 62, 20157 Milano, Italy, ¶ Commissariat à
l'Energie Atomique, Laboratoire de Transgénèse et
Différenciation Cellulaire, Département de Biologie
Moléculaire et Structurale, 17 rue des Martyrs, 38054 Grenoble,
France, and Facoltà di Farmacologia, Università
degli Studi di Milano, Via Vanvitelli 32, 20129 Milano, Italy
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