Enhancement of Endothelial Cell Migration and in Vitro Tube Formation by Tap20, a Novel β5 Integrin–Modulating, Pkcθ-Dependent Protein

Abstract

Migration, proliferation, and tube formation of endothelial cells are regulated by a protein kinase C isoenzyme PKCθ. A full-length cDNA encoding a novel 20-kD protein, whose expression was PKCθ-dependent, was identified in endothelial cells, cloned, characterized, and designated as theta-associated protein (TAP) 20. Overexpression of TAP20 decreased cell adhesion and enhanced migration on vitronectin and tube formation in three-dimensional culture. An antiintegrin αvβ5 antibody prevented these TAP20 effects. Overexpression of TAP20 also decreased focal adhesion formation in αvβ3-deficient cells. The interaction between TAP20 and β5 integrin cytoplasmic domain was demonstrated by protein coprecipitation and immunoblotting. Thus, the discovery of TAP20, which interacts with integrin β5 and modulates cell adhesion, migration, and tube formation, further defines a possible pathway to angiogenesis dependent on PKCθ.